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Growth Hormone Action in Somatostatin Neurons Regulates Anxiety and Fear Memory

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Autor(es):
dos Santos, Willian O. ; Juliano, Vitor A. L. ; Chaves, Fernanda M. ; Vieira, Henrique R. ; Frazao, Renata ; List, Edward O. ; Kopchick, John J. ; Munhoz, Carolina D. ; Donato, Jose, Jr.
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF NEUROSCIENCE; v. 43, n. 40, p. 14-pg., 2023-10-04.
Resumo

Dysfunctions in growth hormone (GH) secretion increase the prevalence of anxiety and other neuropsychiatric diseases. GH receptor (GHR) signaling in the amygdala has been associated with fear memory, a key feature of posttraumatic stress disorder. However, it is currently unknown which neuronal population is targeted by GH action to influence the development of neuropsychiatric diseases. Here, we showed that approximately 60% of somatostatin (SST)-expressing neurons in the extended amygdala are directly responsive to GH. GHR ablation in SST-expressing cells (SST Delta GHR mice) caused no alterations in energy or glucose metabolism. Notably, SSTDGHR male mice exhibited increased anxiety-like behavior in the light-dark box and elevated plus maze tests, whereas SSTDGHR females showed no changes in anxiety. Using auditory Pavlovian fear conditioning, both male and female SSTDGHR mice exhibited a significant reduction in fear memory. Conversely, GHR ablation in SST neurons did not affect memory in the novel object recognition test. Gene expression was analyzed in a micro punch comprising the central nucleus of the amygdala (CEA) and basolateral (BLA) complex. GHR ablation in SST neurons caused sex-dependent changes in the expression of factors involved in synaptic plasticity and function. In conclusion, GHR expression in SST neurons is necessary to regulate anxiety in males, but not female mice. GHR ablation in SST neurons also decreases fear memory and affects gene expression in the amygdala, although marked sex differences were observed. Our findings identified for the first time a neurochemically-defined neuronal population responsible for mediating the effects of GH on behavioral aspects associated with neuropsychiatric diseases. (AU)

Processo FAPESP: 20/01318-8 - Sistema nervoso central como um alvo do hormônio do crescimento para a regulação de múltiplas funções biológicas
Beneficiário:Jose Donato Junior
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 17/21854-9 - Estudo dos efeitos de citocinas pró- e anti-inflamatórias sobre propriedades biofísicas de neurônios POMC e AgRP do núcleo arqueado do hipotálamo
Beneficiário:Fernanda Machado Chaves
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 19/21707-1 - Influência da privação alimentar na excitabilidade de neurônios que expressam o gene Kiss1
Beneficiário:Renata Frazão
Modalidade de apoio: Auxílio à Pesquisa - Regular