Reduced numbers of dopamine neurons in the substantia nigra pars compacta and ventral tegmental area of rats fed an n-3 polyunsaturated fatty acid-deficient diet: A stereological study

Abstract

Inadequate dietary n-3 polyunsaturated fatty acid (PUFA) content is associated with altered function of the CNS dopamine systems. In this study, the effects of dietary n-3 PUFA content was determined on dopamine cell number and morphology. Adult (postnatal day 70), male, Long-Evans rats were raised from conception on diets containing adequate (control) or negligible n-3 PUFAs. The number and morphology of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta and ventral tegmental area were determined stereologically. The number of tyrosine hydroxylase-positive cells in rats fed the n-3 PUFA-deficient diet was 33.9% lower in the substantia nigra pars compacta and 33.7% lower in the ventral tegmental area than in those fed the control diet (P<0.05); however, the volume of tyrosine hydroxylase-positive cell bodies was not different between diet groups in either brain region. Rats fed the n-3 PUFA-deficient diet also exhibited dendritic depletion and isolation of tyrosine hydroxylase-positive cells compared to rats fed the control diet, which had clustering of tyrosine hydroxylase-positive cells and extensive dendritic arborization. These findings support a role for n-3 PUFAs in the survival of dopamine neurons and suggest that altered dopamine cell number, as well as function, contributes to the behavioral effects observed in rats raised on n-3 PUFA-deficient diets.

Transgenic conversion of omega-6 into omega-3 fatty acids in a mouse model of Parkinson's disease

“…However, these observations are in agreement with previous studies demonstrating that n -3 PUFA-defi cient rats show increased striatal and prefrontal cortical DA levels ( 38,39 ) along with a reduced number of DAergic neurons in the SNpc and in the ventral tegmental area ( 40 ). This result reinforces the assertion that n -3 PUFAs have a strong impact on the DAergic system per se, as proposed by several authors [see review ( 41 )].…”

Short-term oral atrazine exposure alters the plasma metabolome of male C57BL/6 mice and disrupts α-linolenate, tryptophan, tyrosine and other major metabolic pathways

“…For example, PUFAs have the ability to modulate the expression, properties, and action of dopamine and serotonin, especially during the perinatal period when maximal brain growth and development takes place (Das 2013). Chronic imbalance of PUFAs induces abnormalities in dopamine and serotonin neurotransmission in adult rats (Delion et al 1996) and exposure of rats to PUFA-deficient diet from postnatal day 0 to 70 reduces the number of dopamine neurons in the substantia nigra pars compacta and ventral tegmental area (Ahmad et al 2008). Clinical plasma metabolomic analyses show that linoleic acid and α-linolenic acid metabolic pathways are disrupted in patients with amnestic mild cognitive impairment and with Alzheimer's disease (Wang et al 2014).…”

Dietary Omega-3 Fatty Acids Modulate Large-Scale Systems Organization in the Rhesus Macaque Brain

“…Children with attentiondeficit hyperactivity disorder (ADHD) have shown low blood levels of DHA and other essential fatty acids (for review, see Raz and Gabis (2009)), whereas -3FA deficiency in rodents and juvenile nonhuman primates has been reported to increase activity and stereotypy consistent with an ADHD-like behavioral pattern (Reisbick et al, 1994;Levant et al, 2010). On a cellular level, low levels of -3FA during prenatal and postnatal development lead to changes in neurotransmitter metabolism, particularly in brain areas such as the prefrontal cortex that underlie complex cognitive functions (Delion et al, 1996;Ahmad et al, 2008). The period of "exuberant" synaptogenesis occurring in the first two postnatal years demands the incorporation of large amounts of DHA into synaptic membranes and corresponds with a surge in brain DHA accretion (Martinez, 1992).…”