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1.
Bull Exp Biol Med ; 175(6): 810-813, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37979021

RESUMO

In the cerebellum, hippocampus, and prefrontal cortex of mature male Wistar rats with trained spatial navigational skill in the Morris water maze, the transcriptional activity the NAPA gene that regulates the transport and secretion of synaptic vesicles, release of neurotransmitters, and protein degradation was determined by real-time PCR. Animals subjected to forced swimming in a time-matched regime (active control) and naïve rats were used as the comparison groups. Suppression of NAPA gene activity was found in the hippocampus and cerebellum of the active control group, while navigation skill training led to a significant increase in gene expression in all brain structures under study. The findings suggest the existence of specific mechanisms regulating NAPA gene activity during the formation of spatial memory and adaptive behavior under stress conditions.


Assuntos
Encéfalo , Memória Espacial , Animais , Masculino , Ratos , Encéfalo/metabolismo , Expressão Gênica , Hipocampo/metabolismo , Aprendizagem em Labirinto/fisiologia , Ratos Wistar , Memória Espacial/fisiologia , Natação , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida/genética
2.
Bull Exp Biol Med ; 174(1): 18-21, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36437318

RESUMO

We studied the effects of chronic intranasal administration of amyloidogenic fibrils of the proinflammatory protein S100A9 alone or in combination with glutamate antibodies on the expression of the neuregulin-1 gene (NRG1), a regulator of various physiological processes, in particular, regulation of neurogenesis and apoptosis, in the hippocampus, prefrontal cortex, and cerebellum of aging C57BL/6 mice under conditions of long-term memory disturbances. Under conditions of amnesia induced by S100A9 fibrils, pronounced (>90%) blockade of the expression of the NRG1 gene was found in all cerebral structures. Glutamate antibodies prevented/corrected disturbances in the cerebral expression of the NRG1 gene, thereby maintaining the activity of the NRG1/ErbB molecular signaling system, probably associated with the formation of spatial memory.


Assuntos
Cérebro , Transtornos da Memória , Neuregulina-1 , Memória Espacial , Animais , Camundongos , Ácido Glutâmico/imunologia , Ácido Glutâmico/metabolismo , Camundongos Endogâmicos C57BL , Neuregulina-1/genética , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Envelhecimento , Proteínas Amiloidogênicas/farmacologia , Calgranulina B/farmacologia , Anticorpos/administração & dosagem , Receptores ErbB/metabolismo
3.
Bull Exp Biol Med ; 172(1): 18-21, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34796426

RESUMO

Proinflammatory S100A9 protein is a promoter of inflammation-linked neurodegeneration and the Tnfrsf1A gene encodes the TNF receptor 1A that binds TNFα to function as a regulator of inflammation. We studied the effects of chronic intranasal administration of in vitro prepared S100A9 fibrils alone or in combination with anti-glutamate antibodies on the expression of the Tnfrsf1A gene in the hippocampus, prefrontal cortex, and cerebellum of aging C57BL/6 mice under conditions of impaired spatial memory. A differential cerebral pattern of Tnfrsf1A gene activity and its modification by S100A9 fibrillar structures were observed: inhibition of Tnfrsf1A gene expression in the hippocampus and cerebellum and its activation in the prefrontal cortex. Anti-glutamate antibodies normalized the expression of the Tnfrsf1A gene in the prefrontal cortex by affecting the TNF signaling pathway and preventing the development of inflammation.


Assuntos
Envelhecimento/fisiologia , Amnésia/patologia , Calgranulina B/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/biossíntese , Memória Espacial/fisiologia , Animais , Anticorpos/imunologia , Cerebelo/metabolismo , Ácido Glutâmico/imunologia , Hipocampo/metabolismo , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Navegação Espacial/fisiologia , Fator de Necrose Tumoral alfa/metabolismo
4.
Bull Exp Biol Med ; 171(1): 19-22, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34046788

RESUMO

We analyzed delayed effect of intranasal administration of anti-glutamate antibodies on mnestic function and tissue concentrations of neurotransmitters in the hippocampus and prefrontal cortex in aging C57BL/6 mice. It was found that after 14-day administration of anti-glutamate antibodies, improvement of the passive avoidance conditioning persisted for 7 days after the treatment was discontinued. In 7 days after discontinuation of treatment, increased content of dopamine and its metabolites as well as aspartic acid and taurine was observed in the hippocampus of mice treated with anti-glutamate antibodies. In the prefrontal cortex, administration of anti-glutamate antibodies had no effect on the levels of neurotransmitters, but increased the concentration of glutamate.


Assuntos
Ácido Aspártico , Ácido Glutâmico , Envelhecimento , Animais , Ácido Aspártico/metabolismo , Ácido Aspártico/farmacologia , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
5.
Bull Exp Biol Med ; 169(1): 5-8, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32474668

RESUMO

Intranasal administration of antibodies to glutamate in a dose of 250 µg/kg for two weeks facilitated spatial learning and memory formation in the Morris water maze in aging C57BL/6 mice. In animals treated with glutamate antibodies, the content of serotonin and dopamine metabolites 3-MT and HVA in the hippocampus decreased, but no changes in the metabolism of neurotransmitter acids were revealed. In the prefrontal cortex, dopamine level decreased and the content of its metabolite DOPAC increased; in parallel, an increase in excitatory and inhibitory amino acids (aspartic acid, glutamate, glycine, taurine, and GABA) was observed.


Assuntos
Anticorpos/farmacologia , Ácido Glutâmico/imunologia , Memória Espacial/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Envelhecimento/psicologia , Animais , Comportamento Animal/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Teste do Labirinto Aquático de Morris
6.
Bull Exp Biol Med ; 166(3): 326-329, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30627908

RESUMO

Chronic intranasal administration of antibodies to glutamate to aging C57Bl/6 mice improved passive avoidance conditioning, had no effect on horizontal and vertical locomotor activity, but slowed locomotion in the open-field test. Administration of antibodies to glutamate increased the content of dopamine and its metabolites in mouse hippocampus, but had no effect on the metabolism of neurotransmitter amino acids. In the frontal cortex, antibodies to glutamate did not affect neurotransmitter metabolism, but increased the level of both excitatory and inhibitory amino acids without changing their ratio.


Assuntos
Envelhecimento/fisiologia , Anticorpos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/metabolismo , Memória/efeitos dos fármacos , Administração Intranasal , Animais , Anticorpos/química , Ácido Aspártico/metabolismo , Aprendizagem da Esquiva/fisiologia , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Dopamina/metabolismo , Antagonistas de Aminoácidos Excitatórios/química , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiologia , Glicina/metabolismo , Haptenos/química , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Ácido Hidroxi-Indolacético/metabolismo , Imunoconjugados/química , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Coelhos , Serotonina/metabolismo , Soroalbumina Bovina/química , Ácido gama-Aminobutírico/metabolismo
7.
Bull Exp Biol Med ; 162(4): 430-432, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28239790
8.
Eur J Pain ; 21(4): 668-680, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27862616

RESUMO

BACKGROUND: Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side-effects. Localized therapy may curtail such side-effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain. METHODS: Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/w) was applied three times daily on the ipsilateral or contralateral plantar surface of the hind-paw, whereas in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/kg) for 30 days. Tests for static- and dynamic-mechano-allodynia [paw withdrawal threshold (PWT) to von Frey filament application and latency (PWL) to light brushing], cold-allodynia [paw withdrawal duration (PWD) to acetone], heat- (PWL and PWD) and mechano-hyperalgesia (PWD to pin prick) were utilized to assess pain, whereas effects on locomotion (open field) and motor balance (rotarod and footprint analysis) were measured on days 5-30 post surgery. RESULTS: Topical application of gabapentin gel ipsilaterally but not contralaterally alleviated CCI-induced static- (days 10-30) and dynamic-allodynia (days 15-30), suppressed cold-allodynia (days 10-30), heat- (days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action. Systemic gabapentin exhibited similar pain profiles but was associated with motor impairment. The gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects. CONCLUSIONS: These outcomes disclose an expedient pharmacological validation of the effectiveness of topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the CCI-induced neuropathic pain model. They also advocate further clinical studies on topical gabapentin with regard to certain neuropathic pain syndromes. SIGNIFICANCE: Systemic gabapentin neuropathic pain management carries side-effects ostensibly preventable by localized therapy. This study validates the effectiveness potential of a topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the chronic constriction injury-induced neuropathic pain model.


Assuntos
Aminas/uso terapêutico , Analgésicos/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Neuropatia Ciática/tratamento farmacológico , Ácido gama-Aminobutírico/uso terapêutico , Administração Tópica , Aminas/administração & dosagem , Analgésicos/administração & dosagem , Animais , Constrição Patológica , Ácidos Cicloexanocarboxílicos/administração & dosagem , Modelos Animais de Doenças , Gabapentina , Masculino , Atividade Motora/efeitos dos fármacos , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ácido gama-Aminobutírico/administração & dosagem
9.
Dement Geriatr Cogn Disord ; 18(2): 165-71, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15211072

RESUMO

We have found an increased level of serum antibodies to the prefibrillar structures of both Abeta(25-35) peptide and human lysozyme in Alzheimer's disease (AD) patients compared to age-matched controls, indicating that autoimmunity is implicated in AD. In the serum of AD patients with a long-term duration (>15 years) the titer of serum antibodies to aggregates of Abeta(25-35) peptide increased by approximately 5-fold, whilst the antibody titer to lysozyme protofilaments decreased by approximately 8-fold compared to patients with AD duration of <5 years. The content of immunoglobulins of the A, G and M types declined, particularly in AD duration of >15 years. An increase in the concentration of immune complexes and higher lysozyme activity was detected in the serum of all patients and this was suggestive of an inflammatory reaction. We propose that the autoimmune response to different amyloid structures in AD can be viewed as a clearance pathway targeting amyloid development. Autoimmune response can be exploited as a marker of ongoing protein aggregation and hence be used as a diagnostic feature of AD.


Assuntos
Doença de Alzheimer/imunologia , Peptídeos beta-Amiloides/imunologia , Autoanticorpos/sangue , Angiopatia Amiloide Cerebral/imunologia , Doenças do Complexo Imune/imunologia , Muramidase/imunologia , Fragmentos de Peptídeos/imunologia , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Amiloide/imunologia , Complexo Antígeno-Anticorpo/sangue , Encéfalo/patologia , Angiopatia Amiloide Cerebral/diagnóstico , Diagnóstico Diferencial , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Doenças do Complexo Imune/diagnóstico , Doenças do Complexo Imune/genética , Imunoglobulinas/sangue , Imageamento por Ressonância Magnética , Entrevista Psiquiátrica Padronizada , Microscopia de Força Atômica , Valores de Referência , Tomografia Computadorizada por Raios X
10.
J Pharm Pharmacol ; 54(7): 885-95, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12162706

RESUMO

This overview has attempted to highlight the brain regions associated with reward, and the pathways and neurotransmitters responsible for communication between these regions. Work conducted in this field has shown that stimulants and opioids, despite interactions with different receptor types and different neurotransmitter reuptake transporters, appear to share a common action on brain reward pathways. Their effects on these pathways (the distinct brain regions making up the mesocorticolimbic dopaminergic system) are predominantly mediated through changes in dopamine neurotransmission, and compounds aimed at selectively modulating these effects may form the basis of drugs to treat addiction. Other transmitters such as GABA, acetylcholine and serotonin inevitably have a role to play in reward, although at present the exact nature of their effects remains unclear. Diverging from manipulating the CNS directly as a management strategy for dependence, it might be possible to exploit the immune system to prevent administered psychostimulants penetrating the brain, but antibody saturation and specificity are problematic.


Assuntos
Adaptação Fisiológica , Encéfalo/fisiologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Relação Dose-Resposta a Droga , Humanos , Modelos Biológicos
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