RESUMO
Mothers who consume alcohol during pregnancy may cause a neurotoxic syndrome defined as fetal alcohol spectrum disorder (FASD) in their offspring. This disorder is characterized by reduction in brain size, cognitive deficits and emotional/social disturbances. These alterations are thought to be caused by an alcohol-induced increase in apoptosis during neurodevelopment. Little is known about neuroapoptosis in the central extended amygdala and the pyriform cortex, which are key structures in emotional/social behaviors. The goal of this study was to determine the vulnerability of neuroapoptotic alcohol effects in those areas. Rats were administered alcohol (2.5g/kg s.c. at 0 and 2h) or saline on postnatal day (PND) 7, 15 and 20. The Amino-cupric-silver technique was used to evaluate neurodegeneration and immunohistochemistry to detect activated caspases 3-8 and 9 at 2h, 4, 6, 8, 12 and 24h after drug administration. We measured blood alcohol levels each hour, from 2 to 8h post second administration of alcohol in each of the ages studied. Results showed alcohol induced apoptotic neurodegeneration in the central extended amygdala on PND 7 and 15, and pyriform cortex on PND 7, 15 and 20. These structures showed activation of caspase 3 and 9 but not of caspase 8 suggesting that alcohol-induced apoptosis could occur by the intrinsic pathway. The pharmacokinetic differences between ages did not associate with the neurodegeneration age dependence. In conclusion, these limbic areas are damaged by alcohol, and each one has their own window of vulnerability during the postnatal period. The possible implications in emotional/social features in FASD are discussed.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/patologia , Morte Celular/efeitos dos fármacos , Etanol/farmacologia , Condutos Olfatórios/efeitos dos fármacos , Condutos Olfatórios/patologia , Animais , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Depressores do Sistema Nervoso Central/sangue , Depressores do Sistema Nervoso Central/farmacologia , Etanol/sangue , Feminino , Transtornos do Espectro Alcoólico Fetal/patologia , Humanos , Masculino , Degeneração Neural/induzido quimicamente , Degeneração Neural/patologia , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/patologia , Ratos , Ratos WistarRESUMO
INTRODUCTION: since middle of the 20th century the importance of amygdala in epilepsy it has suggested, although the basic mechanisms of this participation are still unknown. This ignorance increases when the different subdivisions of amygdala are considered, especially the medial amygdala. In this work we assess the involvement of the medial extended amygdala in an animal model of epilepsy and the consequences of its application in this brain structure. MATERIAL AND METHODS: forty eight adult Wistar male rats were used, of which 24 of them received i.p. injections of pentylenetetrazole, and 24 (controls) were injected with saline. After 2, 6, 12 and 24 h survival, animals were fixed; the brains were sectioned serially and stained for fos (immunochemistry) and for neuronal death with the A-Cu-Ag technique. Data were analysed using two-way ANOVA followed by the Fisher post hoc test. RESULTS: very few or no fos-immunoreactive neurons were seen in control animals. In experimental animals, fos was rapidly induced in structures of medial extended amygdala with peak levels at 2 h. Marked fos immunoreactivity persisted up to 12 h followed by a gradual return to baseline at 24 h. However, status epilepticus did not induced neuronal death. CONCLUSIONS: these results show involvement of medial extended amygdala in epileptic mechanisms with an inhibitory component. However, neuronal death is not a consequence of status epilepticus-induced by pentylentetrazole.
Assuntos
Tonsila do Cerebelo/citologia , Convulsivantes/farmacologia , Epilepsia/fisiopatologia , Neurônios/efeitos dos fármacos , Pentilenotetrazol/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/patologia , Tonsila do Cerebelo/fisiologia , Animais , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Humanos , Masculino , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Neurônios/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos WistarRESUMO
Sex hormones contribute to modulating brain functions throughout the life span. It has been suggested that estrogen prevents neuronal loss in different areas of the CNS such as the hippocampus. However there are less consistent data on its effects on the amygdala. Kainic acid (KA) is used to produce seizures that mimic those of temporal lobe epilepsy in humans. At high doses in animal models, KA induces neurotoxicity, particularly in the medial amygdaloid nuclei (MeA). It is uncertain whether the gonadal hormones are protective or not against this neurotoxicity in the MeA. Here we show that a single dose of KA induces neurodegeneration in the subnuclei of the MeA of rats with different degrees of intensity in males and females. A differential neuroprotective effect of the gonadal hormones was also observed. In diestrous rats, massive neuronal death similar to that in the ovariectomized females was detected. MeA neurons of proestrous rats, like the ovariectomized treated with estrogen, were significantly less affected by the KA. Testosterone produced a mild neuroprotective action, but dihydrotestosterone did not protect. A similar pattern was observed in all male groups. Together, the results indicate that estrogen protects MeA neurons from KA neurotoxicity. Androgens are only partially neuroprotective, with this effect being found only in testosterone, probably through its conversion to estrogen by aromatase.
Assuntos
Tonsila do Cerebelo/patologia , Hormônios Gonadais/fisiologia , Ácido Caínico , Degeneração Neural/patologia , Tonsila do Cerebelo/efeitos dos fármacos , Androgênios/fisiologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Estrogênios/fisiologia , Feminino , Masculino , Degeneração Neural/induzido quimicamente , Degeneração Neural/prevenção & controle , Neurônios/efeitos dos fármacos , Orquiectomia , Ovariectomia , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/patologia , Convulsões/prevenção & controle , Fatores Sexuais , Testosterona/análogos & derivados , Testosterona/farmacologiaRESUMO
The effect of retinal ablation on qualitative and quantitative changes of calbindin D28k and GABA expression in the contralateral optic tectum was studied in young chicks. Fifteen days old chicks had unilateral retinal ablation and after 7 or 15 days, calbindin expression was analyzed by Western blot and immunocytochemistry. Neuronal degeneration was followed by the amino-cupric silver technique. After 15 days, retinal lesions produced a significant decrease in calbindin immunostaining in the neuropil of layers 5-6 and in the somata of neurons from the layers 8 and 10 of the contralateral tectum, being this effect less marked at 7 days post-lesion. Double staining revealed that 50-60% of cells in the layers 8 and 10 were calbindin and GABA positive, 30-45% were only calbindin positive and 5-10% were only GABAergic neurons. Retinal ablation also produced a decrease in the GABA expression at either 7 or 15 days after surgery. At 7 days, dense silver staining was observed in the layers 5-6 from the optic tectum contralateral to the retinal ablation, which mainly represented neuropil that would come from processes of retinal ganglion cells. Tectal neuronal bodies were not stained with silver, although some neurons were surrounded by coarse granular silver deposits. In conclusion, most of calbindin molecules are present in neurons of the tectal GABAergic inhibitory circuitry, whose functioning apparently depends on the integrity of the visual input. A possible role of calbindin in the control of intracellular Ca2+ in neurons of this circuit when the visual transmission arrives to the optic tectum remains to be studied.
Assuntos
Galinhas , Retina/fisiologia , Degeneração Retiniana/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Colículos Superiores/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Western Blotting , Calbindinas , Denervação , Técnicas Imunoenzimáticas , Retina/patologia , Retina/cirurgia , Degeneração Retiniana/etiologia , Degeneração Retiniana/patologiaRESUMO
Neurons that accompany the stria terminalis as it loops over the internal capsule have been termed collectively the supracapsular bed nucleus of the stria terminalis (BSTS). They form two cell columns, a lateral column and a considerably smaller medial column. The lateral column merges rostrally with the lateral bed nucleus of the stria terminalis and caudally with the central amygdaloid nucleus (central extended amygdala components). The medial column is continuous with the medial bed nucleus of the stria terminalis and the medial amygdaloid nucleus (medial extended amygdala districts). The connections of the BSTS were investigated in the rat by placing injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) or retrograde tracers in different parts of the extended amygdala or in structures related to the extended amygdala. BSTS inputs and outputs were identified, respectively, by the presence of varicose fibers and retrogradely labeled neurons within the stria terminalis. The results suggest that the medial-to-lateral compartmentalization of BSTS neurons reflects their close alliance with the medial and central divisions of the extended amygdala. The medial BSTS contains primarily elements that correspond to the posterodorsal part of the medial amygdaloid nucleus and the medial column of the posterior division of the medial bed nucleus of the stria terminalis, and the lateral BSTS contains elements that correspond to the medial and lateral parts of the central amygdaloid nucleus and lateral bed nucleus of the stria terminalis. These results add strong support to the concept of the extended amygdala as a ring-like macrostructure around the internal capsule, and they are of theoretical interest for the understanding of the organization of the basal forebrain.
Assuntos
Vias Aferentes/anatomia & histologia , Tonsila do Cerebelo/anatomia & histologia , Núcleos Septais/anatomia & histologia , Vias Aferentes/química , Tonsila do Cerebelo/química , Animais , Glicoproteínas/análise , Fito-Hemaglutininas/análise , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Ratos Wistar , Núcleos Septais/químicaRESUMO
Several studies have reported transient expression of tyrosine hydroxylase in a subpopulation of neurons in the bed nucleus of stria terminalis of preadolescent rats. The tyrosine hydroxylase immunoreactive (TH) neurons, which are of small to medium size and often display a typical bipolar configuration, are confined to the intermediate part of the lateral bed nucleus. By the use of a combination of experimental tracer techniques and immunocytochemical methods, we have demonstrated that these neurons receive a significant number of amygdaloid afferents, which establish mostly symmetric synaptic contacts on the cell bodies and sparsely spined dendritic shafts of the TH neurons. TH neurons also receive a small number of tyrosine hydroxylase-positive terminals of unspecified origin.
Assuntos
Tonsila do Cerebelo/fisiologia , Neurônios/química , Tirosina 3-Mono-Oxigenase/análise , Animais , Tamanho Celular , Imuno-Histoquímica , Masculino , Ratos , Fatores de TempoRESUMO
A new amino-cupric silver protocol is described for detection of neuronal degeneration. We describe its selectivity in visualizing both early and semiacute degeneration after intracerebral or systemic administration of a variety of neurotoxicants in rats, and after transient ischemic episodes in gerbils. As early as 5 min after physical trauma, or 15 min following either intrastriatal injections of glutamate analogs or exposure to ischemic episodes, neuronal silver staining was evident at primary sites of trauma (i.g. injection sites) and at hodologically related secondary sites. With intoxication by peripheral injections of trimethyltin (IP) or intracerebral injections of Doxorubicin, reproducible patterns of degeneration are demonstrable after 24 h or after 9-13 days, respectively. The amino-cupric silver method permits simultaneous detection of all neuronal compartments against a clear background. Degeneration in the neuronal cell bodies, dendrites, axons and terminals, as well as the recruitment of new structures in a progressive pathologic process, could be accurately followed. The inclusion of new reagents increased the sensitivity vis-à-vis previous versions of the cupric-silver method. The advantages and disadvantages of the current method in comparison with other means of neurotoxic assessment are discussed in detail, with special emphasis on its unique ability to discriminate irreversible degenerative phenomena and degeneration of axonal components in cases where the cell body remains apparently intact. The amino-cupric silver method is an especially useful tool for surveying neuronal damage in basic neuroscience investigations and in neuropathologic and neurotoxic assessment.
Assuntos
Degeneração Neural/efeitos dos fármacos , Neurotoxinas/toxicidade , Coloração e Rotulagem/métodos , Animais , Tatus , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Isquemia Encefálica/patologia , Feminino , Gerbillinae , Cobaias , Haplorrinos , Hipóxia/patologia , Masculino , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/patologia , Ácido Quinolínico/toxicidade , Coelhos , Ratos , Prata , Traumatismos do Sistema Nervoso , Compostos de Trimetilestanho/toxicidadeRESUMO
The amounts of time spent by females in the sector of an open field close to the cage housing a normal male or a castrated male were measured in order to quantitate the tendency of the female to reach physical proximity to a sexually active male (androtropism). Intact proestrous or ovariectomized females primed with 100 micrograms of estradiol benzoate/kg b. wt. (EB) or EB plus 2 mg progesterone/kg b. wt. (P) spent significantly more time close to the sexually active (intact) male than in the proximity of the orchidectomized male. In order to determine whether olfactory clues were sufficient for female rats to distinguish between intact and castrated males, the males were removed from the stimulus cages, leaving the soiled bedding in place. Ovariectomized rats primed with EB or EB plus P clearly preferred proximity to the cage where the intact male had been living. No preference was evident after transection of olfactory nerves in proestrous rats or in ovariectomized rats primed with EB plus P. Resection of the vomeronasal organ also suppressed preference. These results indicate that olfactory input is necessary and sufficient for androtropism to occur, and suggest that the accessory olfactory system is involved in the analysis of olfactory signals used by female rats to identify the endocrine status of prospective sexual partners. In a different group of animals, it was demonstrated that destruction of the posteromedial cortical amygdaloid nucleus also suppressed preference for the intact male. It is proposed that this structure serves as a relay station for the analysis and integration of olfactory input significant for the motivational control of sexual behavior in the female rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Nível de Alerta/fisiologia , Sistema Nervoso Central/fisiologia , Estro/fisiologia , Condutos Olfatórios/fisiologia , Comportamento Sexual Animal/fisiologia , Olfato/fisiologia , Tonsila do Cerebelo/fisiologia , Animais , Mapeamento Encefálico , Feminino , Masculino , Mucosa Nasal/fisiologia , Bulbo Olfatório/fisiologia , Nervo Olfatório/fisiologia , Ratos , Meio SocialRESUMO
A study was made of the control of the hypothalamus and neuroendocrine complex by the specialized receptors: the eye, the ear and the olfactory complex. The ancient and modern evidence that light, acting on the optic system, can influence hypothalamic, hypophyseal, endocrine reactions was reviewed and the recently acquired evidence that an optic-hypothalamic-autonomic-pineal-hypothalamic circuit exists which controls liberation of "releasing hormones". Evidence was presented to show that the ear and eye, extero-and interoceptive influences affect lactation and oxytocin secretion by action through the hypothalamus. It was also shown that electrochemical stimulation of the olfactory bulbs can affect both sexual behavior and gonadotropin secretion. Finally, it was shown that the olfactory system exerts some control over water intake, sodium appetite and antidiuretic hormone secretion. Progress in a long term cooperative study of the role of exteroceptor control of neuroendocrine functions was reported.
Assuntos
Vias Auditivas/fisiologia , Glândulas Endócrinas/fisiologia , Hipotálamo/fisiologia , Células Receptoras Sensoriais/fisiologia , Vias Visuais/fisiologia , Animais , Estimulação Elétrica , Feminino , Cobaias , Lactação , Condutos Olfatórios/fisiologia , Ocitocina/metabolismo , Gravidez , Ratos , Reprodução , Paladar/fisiologia , Vasopressinas/metabolismo , Equilíbrio HidroeletrolíticoRESUMO
A study was made of the control of the hypothalamus and neuroendocrine complex by the specialized receptors: the eye, the ear and the olfactory complex. The ancient and modern evidence that light, acting on the optic system, can influence hypothalamic, hypophyseal, endocrine reactions was reviewed and the recently acquired evidence that an optic-hypothalamic-autonomic-pineal-hypothalamic circuit exists which controls liberation of [quot ]releasing hormones[quot ]. Evidence was presented to show that the ear and eye, extero-and interoceptive influences affect lactation and oxytocin secretion by action through the hypothalamus. It was also shown that electrochemical stimulation of the olfactory bulbs can affect both sexual behavior and gonadotropin secretion. Finally, it was shown that the olfactory system exerts some control over water intake, sodium appetite and antidiuretic hormone secretion. Progress in a long term cooperative study of the role of exteroceptor control of neuroendocrine functions was reported.
RESUMO
A study was made of the control of the hypothalamus and neuroendocrine complex by the specialized receptors: the eye, the ear and the olfactory complex. The ancient and modern evidence that light, acting on the optic system, can influence hypothalamic, hypophyseal, endocrine reactions was reviewed and the recently acquired evidence that an optic-hypothalamic-autonomic-pineal-hypothalamic circuit exists which controls liberation of [quot ]releasing hormones[quot ]. Evidence was presented to show that the ear and eye, extero-and interoceptive influences affect lactation and oxytocin secretion by action through the hypothalamus. It was also shown that electrochemical stimulation of the olfactory bulbs can affect both sexual behavior and gonadotropin secretion. Finally, it was shown that the olfactory system exerts some control over water intake, sodium appetite and antidiuretic hormone secretion. Progress in a long term cooperative study of the role of exteroceptor control of neuroendocrine functions was reported.