Role for Histone Deacetylation in Traumatic Brain Injury-Induced Deficits in Neuropeptide Y in Arcuate Nucleus: Possible Implications in Feeding Behavior.
Neuroendocrinology
; 111(12): 1187-1200, 2021.
Article
em En
| MEDLINE
| ID: mdl-33291119
ABSTRACT
INTRODUCTION:
Repeated traumatic events result in long-lasting neuropsychiatric ailments, including neuroendocrine imbalances. Neuropeptide Y (NPY) in the arcuate nucleus (Arc) is an important orexigenic peptide. However, the molecular underpinnings of its dysregulation owing to traumatic brain injury remain unknown.METHODS:
Rats were subjected to repeated mild traumatic brain injury (rMTBI) using the closed head weight-drop model. Feeding behavior and the regulatory epigenetic parameters of NPY expression were measured at 48 h and 30 days post-rMTBI. Further, sodium butyrate (SB), a pan-histone deacetylase (HDAC) inhibitor, was administered to examine whether histone deacetylation is involved in NPY expression post-rMTBI.RESULTS:
The rMTBI attenuated food intake, which was coincident with a decrease in NPY mRNA and protein levels in the Arc post-rMTBI. Further, rMTBI also reduced the mRNA levels of the cAMP response element-binding protein (CREB) and CREB-binding protein (CBP) and altered the mRNA levels of the various isoforms of the HDACs. Concurrently, the acetylated histone 3-lysine 9 (H3-K9) levels and the binding of CBP at the NPY promoter in the Arc of the rMTBI-exposed rats were reduced. However, the treatment with SB corrected the rMTBI-induced deficits in the H3-K9 acetylation levels and CBP occupancy at the NPY promoter, restoring both NPY expression and food intake.CONCLUSIONS:
These findings suggest that histone deacetylation at the NPY promoter persistently controls NPY function in the Arc after rMTBI. This study also demonstrates the efficacy of HDAC inhibitors in mitigating trauma-induced neuroendocrine maladaptations in the hypothalamus.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comportamento Animal
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Neuropeptídeo Y
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Concussão Encefálica
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Núcleo Arqueado do Hipotálamo
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Ácido Butírico
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Comportamento Alimentar
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Inibidores de Histona Desacetilases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article