n−3 fatty acids prevent impairment of neurogenesis and synaptic plasticity in B-cell activating factor (BAFF) transgenic mice

Abstract

Objective. Autoimmune-prone B-cell activating factor transgenic mice, a mouse model of systemic lupus erythematosus and Sjögren's syndrome exhibit neuroinflammation, anxiety-like phenotype, deficit in adult hippocampal neurogenesis and impaired neurogenesis-dependent and neurogenesis-independent dentate gyrus long-term potentiation. Given that n−3 polyunsaturated fatty acids regulate hippocampal plasticity and inflammatory responses, we investigated whether n−3 polyunsaturated fatty acids-enriched diet might prevent age-dependent hippocampal changes in B-cell activating factor transgenic mice.Methods. B-cell activating factor transgenic mice were fed for 12 weeks with either n−3 polyunsaturated fatty acids-enriched or control diet and we tested the effect of this dietary supplementation on hippocampal inflammation, progenitor cell proliferation and neurogenesis-dependent and neurogenesis-independent long-term potentiation.Results. Dietary supplementation with n−-3 polyunsaturated fatty acids significantly decreased hippocampal microglial activation and increased the density of bromodeoxyuridine and doublecortin-positive newly-formed cells in the subventricular zone of hippocampus. Furthermore, B-cell activating factor transgenic mice fed with n-3 polyunsaturated fatty acids-enriched diet displayed normal long-term potentiation at the medial perforant pathway/dentate gyrus connections.Conclusions. The results indicate that n-3 fatty acids prevent neuroinflammation and deficits of hippocampal plasticity in B-cell activating factor transgenic mice and suggest that increased n-3 fatty acids intake might represent a potential therapeutic option to prevent neuropsychiatric symptoms associated with autoimmune diseases.

Impact of dietary n-3 polyunsaturated fatty acids on cognition, motor skills and hippocampal neurogenesis in developing C57BL/6J mice

“…However, our results obtained by qRT-PCR indicate that synaptic plasticity may be increased at pubertal age in the cortex, while it remains unaffected at adult age. Several studies demonstrated an increased expression of presynaptic and postsynaptic proteins after n-3 PUFA supplementation, hinting at increased synaptogenesis either early on in life or during aging [22,51,86]. Our data on synaptophysin expression led us to hypothesize that synaptogenesis is stimulated at adolescent age on an n-3 PUFA adequate diet and reaches a plateau before adult age.…”

“…Besides, the expression of inflammatory markers remained unaffected by n-3 PUFA availability during development. N-3 PUFA supplementation has been shown to decrease neuroinflammation in immune deprived and aged mice [86,88]. It is not likely that the young, healthy C57BL/6J mice used in our experiments are prone to inflammation at this stage in life, which is supported by the fact that n-3 PUFA availability did not affect inflammatory markers.…”

“…It should be noted that these studies were performed at an earlier age than the immunohistochemical staining in our experiment. Additionally, n-3 PUFA supplementation counteracted the reduction of hippocampal neurogenesis in an immune deprived mouse model [86]. Combined, these data suggest that n-3 PUFA availability may promote earlier neurogenesis, possibly already before pubertal age.…”

“…To our knowledge, this is the first study to show diminished neurogenesis in young adult mice due to altered n-3 PUFA availability during development. Contrarily, several studies have illustrated an increase of neurogenesis after LCPUFA supplementation [58,61,86]. Niculescu et al assessed hippocampal neurogenesis of n-3 PUFA supplemented mice at the end of the lactation period (PND 19) and detected an increase in cell proliferation [58].…”

Effects of Diet on Brain Plasticity in Animal and Human Studies: Mind the Gap

“…For instance, dietary supplementation with n-3 PUFAs restored neurogenic markers in the DG of a mouse model of systemic lupus erythematosus and Sjögren's syndrome, characterised by lower levels of AHN among other biological deficits [181]. Perinatal supplementation with n-3 PUFA also mitigated the impairment in working and short-term memory and altered fear response observed in rats as a consequence of sevoflurane-induced neurotoxicity, likely through decreased apoptosis and enhancement of hippocampal cell proliferation [182].…”