RESUMO
Nutritional status is associated with many neurocognitive diseases. Folate is one of the micronutrients, and its deficiency is associated with clinical outcomes of neurological diseases. Nevertheless, molecular mechanism behind the folate deficiency induced neurological disorders are not well-known. We have hypothesized that folate-deficiency is a cardinal determinant responsible for manifestation of cognitive impairment through inflammation mediated neurodegenerative pathologies. Objective of the current study was to assess whether folate deficiency is associated with cognitive dysfunction or is merely an epiphenomenon and to identify the underlying mechanisms. We developed folate insufficient zebrafish model through intra-peritoneal treatment of methotrexate. T-maze test was carried to assess the spatial learning and memory of the fish. Higher latency of the folate-deprived zebrafishes in the T-maze test is a reflection of altered cognition. This result is supported by declined levels of dopamine and serotonin, neurotransmitters linked with learning and memory. Elevated IL-6 and CRP in peripheral blood, along with increased expression of NF-ĸB in brain indicates manifestation of neuroinflammation. Indeed, together with upregulation of maptb gene it can be implied that folate deficiency acts as a risk factor for neurodegeneration in the form of tauopathies. Furthermore, diminished localisation of synaptopodin, a protein linked to neural plasticity, suggests that neuroinflammation caused by folate deprivation hampers the plasticity of brain. Histological analysis of brain revealed the development of histopathological features including spongiform degeneration and neuronal loss in folate deprived condition. We thus conclude that folate deficiency results in NF-ĸB activation, which through multiple processes mediated by neuroinflammation could lead to cognitive decline.