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1.
J Chem Neuroanat ; 96: 73-78, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30597197

RESUMO

Parkinson's disease (PD) is mainly characterized by a dopamine deficiency accompanied by structural and functional changes in striatal neuronal projections. However, studies have considered PD as a multi-systemic disease in which the neurodegenerative process extends beyond the dopaminergic system. Therefore, the purpose of the present study was to investigate the time-course of serotonergic neuron damage in a progressive model of parkinsonism induced by a low dose of reserpine. Thus, male Wistar rats received 4 (ST, short-treatment of reserpine) or 10 (MT, middle-term treatment of reserpine) subcutaneous injections of vehicle or reserpine (0.1 mg/kg) at a volume of 1 mL/kg body weight, on alternate days. Animals were euthanized 48 h after the last injection for immunohistochemical analysis. After ST, 5-HT immunoreactivity decreased in hippocampal subareas (CA1 and CA3) and medial prefrontal cortex (mPFC) compared to vehicle. Furthermore, animals MT-treated also showed progressive decrease of 5-HT immunoreactivity in CA1 and CA3 subareas. Conversely, a significant increase of 5-HT immunoreactivity was found in mPFC and dorsal raphe nucleus (DRN) in animals submitted to MT when compared to ST exposure. The results showed that, in the repeated low-dose reserpine rat model, variations in the immunoreactivity of 5-HT start early in the course of progressive parkinsonism.


Assuntos
Inibidores da Captação Adrenérgica/toxicidade , Encéfalo/metabolismo , Transtornos Parkinsonianos/metabolismo , Reserpina/toxicidade , Serotonina/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
2.
Brain Res Bull ; 142: 297-303, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30118749

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease related to the dopaminergic system. The etiology is not fully understood, but it is known that PD is a multifactorial disease that involves genetic and environmental factors, including pesticides. One of these, Deltamethrin (DM), has been widely used for vector control in crops, farming, veterinary medicine and domestic pest control. The purpose of the present study was to investigate the effect of DM repeated administration on motor, cognitive and emotional behavior and dopaminergic parameters. Male Wistar rats received 3 intranasal (i.n.) injections of 100 µL (50 µL/nostril) of DM 0.5 µg/µl or Vehicle (saline solution 0.9%), one injection per week. We observed that DM caused memory (novel object recognition task) and emotion (contextual conditioned fear) alterations accompanied by reduction of TH immunoreactivity in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), and increase of TH immunoreactivity in the dorsal striatum. Motor alterations (catalepsy and open field task) were not observed throughout treatment. These findings suggest a possible early disruption of the dopaminergic pathway caused by repeated DM exposure, similar to that observed in early stages of PD.


Assuntos
Emoções/efeitos dos fármacos , Memória/efeitos dos fármacos , Nitrilas/efeitos adversos , Praguicidas/efeitos adversos , Piretrinas/efeitos adversos , Tirosina 3-Mono-Oxigenase/metabolismo , Administração Intranasal , Animais , Emoções/fisiologia , Masculino , Memória/fisiologia , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/etiologia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Parte Compacta da Substância Negra/efeitos dos fármacos , Parte Compacta da Substância Negra/metabolismo , Parte Compacta da Substância Negra/patologia , Distribuição Aleatória , Ratos Wistar , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/metabolismo , Área Tegmentar Ventral/patologia
3.
Neurosci Res ; 121: 54-59, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28288865

RESUMO

The circadian timing system (CTS) anticipates optimal physiological patterns in response to environmental fluctuations, such as light-dark cycle. Since age-related disruption of circadian synchronization is linked to several pathological conditions, we characterized alterations of neurochemical constituents and retinal projections to the major pacemaker of CTS, the suprachiasmatic nucleus (SCN), in adult and aged marmosets. We used intraocular injections of neural tracer Cholera toxin b (CTb) to report age-related reductions in CTb, neuropeptide Y and serotonin immunoreactivities. Considering these projections arise in SCN from nuclei that relay environmental information to entrain the circadian clock, we provide important anatomical correlates to age-associated physiological deficits.


Assuntos
Vias Aferentes/fisiologia , Envelhecimento , Neuropeptídeo Y/metabolismo , Retina/metabolismo , Serotonina/metabolismo , Núcleo Supraquiasmático/metabolismo , Animais , Callithrix , Toxina da Cólera/metabolismo , Densitometria , Masculino , Estatísticas não Paramétricas , Núcleo Supraquiasmático/citologia
4.
J Chem Neuroanat ; 77: 100-109, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27292410

RESUMO

It is widely known that the catecholamine group is formed by dopamine, noradrenaline and adrenaline. Its synthesis is regulated by the enzyme called tyrosine hydroxylase. 3-hydroxytyramine/dopamine (DA) is a precursor of noradrenaline and adrenaline synthesis and acts as a neurotransmitter in the central nervous system. The three main nuclei, being the retrorubral field (A8 group), the substantia nigra pars compacta (A9 group) and the ventral tegmental area (A10 group), are arranged in the die-mesencephalic portion and are involved in three complex circuitries - the mesostriatal, mesolimbic and mesocortical pathways. These pathways are involved in behavioral manifestations, motricity, learning, reward and also in pathological conditions such as Parkinson's disease and schizophrenia. The aim of this study was to perform a morphological analysis of the A8, A9 and A10 groups in the common marmoset (Callithrix jacchus - a neotropical primate), whose morphological and functional characteristics support its suitability for use in biomedical research. Coronal sections of the marmoset brain were submitted to Nissl staining and TH-immunohistochemistry. The morphology of the neurons made it possible to subdivide the A10 group into seven distinct regions: interfascicular nucleus, raphe rostral linear nucleus and raphe caudal linear nucleus in the middle line; paranigral and parainterfascicular nucleus in the middle zone; the rostral portion of the ventral tegmental area nucleus and parabrachial pigmented nucleus located in the dorsolateral portion of the mesencephalic tegmentum. The A9 group was divided into four regions: substantia nigra compacta dorsal and ventral tiers; substantia nigra compacta lateral and medial clusters. No subdivisions were made for the A8 group. These results reveal that A8, A9 and A10 are phylogenetically stable across species. As such, further studies concerning such divisions are necessary in order to evaluate the occurrence of subdivisions that express DA in other primate species, with the aim of characterizing its functional relevance.


Assuntos
Substância Negra/anatomia & histologia , Substância Negra/enzimologia , Tegmento Mesencefálico/anatomia & histologia , Tegmento Mesencefálico/enzimologia , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/anatomia & histologia , Área Tegmentar Ventral/enzimologia , Animais , Comportamento , Callithrix , Imuno-Histoquímica , Aprendizagem , Masculino , Atividade Motora , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Neurônios/ultraestrutura , Núcleos da Rafe/anatomia & histologia , Núcleos da Rafe/citologia , Núcleos da Rafe/fisiologia , Recompensa
5.
Age (Dordr) ; 38(1): 4, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26718202

RESUMO

Aging leads to several anatomical and functional deficits in circadian timing system. In previous works, we observed morphological alterations with age in hypothalamic suprachiasmatic nuclei, one central component of this system. However, there are few data regarding aging effects on other central components of this system, such as thalamic intergeniculate leaflet (IGL). In this context, we studied possible age-related alterations in neurochemical components and retinal projections of rat IGL. For this goal, young (3 months), adult (13 months), and aged (23 months) Wistar rats were submitted to an intraocular injection of neural tracer, cholera toxin subunit b (CTb), 5 days before a tissue fixation process by paraformaldehyde perfusion. Optical density measurements and cell count were performed at digital pictures of brain tissue slices processed by immunostaining for glutamic acid decarboxylase (GAD), enkephalin (ENK), neuropeptide Y (NPY) and CTb, characteristic markers of IGL and its retinal terminals. We found a significant age-related loss in NPY immunoreactive neurons, but not in immunoreactivity to GAD and ENK. We also found a decline of retinal projections to IGL with age. We conclude aging impairs both a photic environmental clue afferent to IGL and a neurochemical expression which has an important modulatory circadian function, providing strong anatomical correlates to functional deficits of the aged biological clock.


Assuntos
Envelhecimento/metabolismo , Ritmo Circadiano , Hipotálamo/química , Neuropeptídeo Y/metabolismo , Retina/química , Núcleo Supraquiasmático/química , Animais , Hipotálamo/citologia , Imuno-Histoquímica , Masculino , Neurônios/citologia , Neurônios/metabolismo , Ratos , Ratos Wistar , Retina/citologia , Núcleo Supraquiasmático/citologia
6.
Psychol. neurosci. (Impr.) ; 6(3): 287-297, July-Dec. 2013. ilus
Artigo em Inglês | LILACS | ID: lil-703092

RESUMO

Animals have neural structures that allow them to anticipate environmental changes and then regulate physiological and behavioral functions in response to these alterations. The suprachiasmatic nucleus of the hypothalamus (SCN) is the main circadian pacemaker in many mammalian species. This structure synchronizes the biological rhythm based on photic information that is transmitted to the SCN through the retinohypothalamic tract. The aging process changes the structural complexity of the nervous system, from individual nerve cells to global changes, including the atrophy of total gray matter. Aged animals show internal time disruptions caused by morphological and neurochemical changes in SCN components. The effects of aging on circadian rhythm range from effects on simple physiological functions to effects on complex cognitive performance, including many psychiatric disorders that influence the well-being of the elderly. In this review, we summarize the effects of aging on morphological, neurochemical, and circadian rhythmic functions coordinated by the main circadian pacemaker, the SCN...


Assuntos
Humanos , Envelhecimento , Núcleo Supraquiasmático , Ritmo Circadiano
7.
Behav Brain Res ; 253: 68-77, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23831411

RESUMO

Studies have suggested that cognitive deficits can precede motor alterations in Parkinson's disease (PD). However, in general, classic animal models are based on severe motor impairment after one single administration of neurotoxins, and thereby do not express the progressive nature of the pathology. A previous study showed that the repeated administration with a low dose (0.1mg/kg) of the monoamine depleting agent reserpine induces a gradual appearance of motor signs of pharmacological parkinsonism in rats. Here, we showed this repeated treatment with reserpine induced a memory impairment (evaluated by the novel object recognition task) before the gradual appearance of the motor signs. Additionally, these alterations were accompanied by decreased tyrosine hydroxylase (TH) striatal levels and reduced number of TH+ cells in substantia nigra pars compacta (SNpc). After 30 days without treatment, reserpine-treated animals showed normal levels of striatal TH, partial recovery of TH+ cells in SNpc, recovery of motor function, but not reversal of the memory impairment. Furthermore, the motor alterations were statistically correlated with decreased TH levels (GD, CA1, PFC and DS) and number of TH+ cells (SNpc and VTA) in the brain. Thus, we extended previous results showing that the gradual appearance of motor impairment induced by repeated treatment with a low dose of reserpine is preceded by short-term memory impairment, as well as accompanied by neurochemical alterations compatible with the pathology of PD.


Assuntos
Cognição/fisiologia , Discinesia Induzida por Medicamentos/psicologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/psicologia , Reserpina , Simpatolíticos , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Catalepsia/induzido quimicamente , Catalepsia/psicologia , Interpretação Estatística de Dados , Imuno-Histoquímica , Masculino , Atividade Motora/efeitos dos fármacos , Doença de Parkinson Secundária/enzimologia , Ratos , Reconhecimento Psicológico/efeitos dos fármacos
8.
Psychol. neurosci. (Impr.) ; 6(3): 287-297, 2013. ilus
Artigo em Inglês | Index Psicologia - Periódicos | ID: psi-61622

RESUMO

Animals have neural structures that allow them to anticipate environmental changes and then regulate physiological and behavioral functions in response to these alterations. The suprachiasmatic nucleus of the hypothalamus (SCN) is the main circadian pacemaker in many mammalian species. This structure synchronizes the biological rhythm based on photic information that is transmitted to the SCN through the retinohypothalamic tract. The aging process changes the structural complexity of the nervous system, from individual nerve cells to global changes, including the atrophy of total gray matter. Aged animals show internal time disruptions caused by morphological and neurochemical changes in SCN components. The effects of aging on circadian rhythm range from effects on simple physiological functions to effects on complex cognitive performance, including many psychiatric disorders that influence the well-being of the elderly. In this review, we summarize the effects of aging on morphological, neurochemical, and circadian rhythmic functions coordinated by the main circadian pacemaker, the SCN.(AU)


Assuntos
Núcleo Supraquiasmático , Envelhecimento , Ritmo Circadiano
9.
Neurosci Lett ; 488(1): 6-10, 2011 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-21055446

RESUMO

Serotonin (5-HT) is involved in the fine adjustments at several brain centers including the core of the mammal circadian timing system (CTS) and the hypothalamic suprachiasmatic nucleus (SCN). The SCN receives massive serotonergic projections from the midbrain raphe nuclei, whose inputs are described in rats as ramifying at its ventral portion overlapping the retinohypothalamic and geniculohypothalamic fibers. In the SCN, the 5-HT actions are reported as being primarily mediated by the 5-HT1 type receptor with noted emphasis for 5-HT(1B) subtype, supposedly modulating the retinal input in a presynaptic way. In this study in a New World primate species, the common marmoset (Callithrix jacchus), we showed the 5-HT(1B) receptor distribution at the dorsal SCN concurrent with a distinctive location of 5-HT-immunoreactive fibers. This finding addresses to a new discussion on the regulation and synchronization of the circadian rhythms in recent primates.


Assuntos
Receptor 5-HT1B de Serotonina/metabolismo , Núcleo Supraquiasmático/metabolismo , Animais , Callithrix/anatomia & histologia , Toxina da Cólera/metabolismo , Diagnóstico por Imagem , Masculino , Vias Visuais/metabolismo
10.
Brain Res ; 1241: 56-61, 2008 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-18817760

RESUMO

The thalamic paraventricular nucleus (PVT) receives afferents from numerous brain areas, including the hypothalamic suprachiasmatic nucleus (SCN), considered to be the major circadian pacemaker. The PVT also sends projections to the SCN, limbic system centers and some nuclei involved in the control of the Sleep-Wake cycle. In this study, we report the identification of a hitherto not reported direct retinal projection to the PVT of the rock cavy, a typical rodent species of the northeast region of Brazil. After unilateral intravitreal injections of cholera toxin subunit B (CTb), anterogradely transported CTb-immunoreactive fibers and presumptive terminals were seen in the PVT. Some possible functional correlates of the present data are briefly discussed, including the role of the PVT in the modulation of the circadian rhythms by considering the reciprocal connections between the PVT and the SCN. The present work is the first to show a direct retinal projection to the PVT of a rodent and may contribute to elucidate the anatomical substrate of the functionally demonstrated involvement of this midline thalamic nucleus in the modulation of the circadian timing system.


Assuntos
Axônios/ultraestrutura , Ritmo Circadiano/fisiologia , Núcleos da Linha Média do Tálamo/citologia , Células Ganglionares da Retina/citologia , Roedores/anatomia & histologia , Vias Visuais/citologia , Animais , Axônios/fisiologia , Mapeamento Encefálico , Toxina da Cólera , Imuno-Histoquímica , Núcleos da Linha Média do Tálamo/fisiologia , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/ultraestrutura , Retina/citologia , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Roedores/fisiologia , Especificidade da Espécie , Coloração e Rotulagem , Núcleo Supraquiasmático/citologia , Núcleo Supraquiasmático/fisiologia , Vias Visuais/fisiologia
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