Anti‐apoptotic role of omega‐3‐fatty acids in developing brain: perinatal hypothyroid rat cerebellum as apoptotic model

International Journal of Developmental Neuroscience - Tập 27 - Trang 377-383 - 2009
Rohit A. Sinha1, Priyanka Khare2, Asit Rai2, Shailendra Kumar Maurya2, Amrita Pathak1, Vishwa Mohan1, Geet Kumar Nagar3, Mohana Krishna Reddy Mudiam4, Madan M. Godbole1, Sanghamitra Bandyopadhyay2
1Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226001, India
2Developmental Toxicology, Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), Lucknow 226001, India
3Endocrinology, Central Drug Research Institute, Lucknow 226001, India
4Analytical Chemistry, Indian Institute of Toxicology Research, Lucknow 226001, India

Tóm tắt

AbstractInadequate maternal intake of omega‐3‐fatty acids (ω3 FAs) causes adverse neurodevelopmental outcome in the progeny; however, their molecular mechanism of action is obscure. Since ω3 FAs are known to inhibit neuronal apoptosis during neuro‐degeneration, we investigated their possible contribution in regulating neuronal apoptosis during brain development. Using rat model of hypothyroidism‐induced neuronal apoptosis, we provide evidence for anti‐apoptotic role of ω3 FAs during cerebellar development. ω3 FAs were supplemented as a mixture of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to pregnant and lactating rats, and primary hypothyroidism was induced by administering methimazole. The cerebella from postnatal day 16 (d16) pups were isolated, and studies on apoptosis were conducted. We observed that ω3 FA‐supplementation significantly reduced DNA fragmentation and caspase‐3 activation in developing cerebellum of hypothyroid pups. The protection provided by ω3 FAs was associated with their ability to prevent increases in the level of pro‐apoptotic basal cell lymphoma protein‐2 (Bcl‐2)‐associated X protein (Bax) in the cerebellum during thyroid hormone (TH) deficiency. ω3 FAs increased the levels of anti‐apoptotic proteins like Bcl‐2 and Bcl‐extra large (Bcl‐xL), known to be repressed in hypothyroidism. ω3 FAs also restored levels of cerebellar phospho (p)‐AKT, phospho‐extracellular regulated kinase (p‐ERK) and phospho‐c‐Jun N‐terminal kinase (p‐JNK), which were altered by hypothyroid insults, without interfering with the expression of TH responsive gene, myelin basic protein (mbp). Taken together, these results supplement an insight into the molecular mechanism of action of ω3 FAs in developing brain that involves regulation of apoptotic signaling pathways under stress.

Tài liệu tham khảo

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International Journal of Developmental Neuroscience

Tập 27

377-383

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