Abstract
Recent evidence indicates the number of dopaminergic neurons in the adult rodent hypothalamus and midbrain is regulated by environmental cues, including photoperiod, and that this occurs via up- or down-regulation of expression of genes and proteins that are important for dopamine (DA) synthesis in extant neurons (‘DA neurotransmitter switching’). If the same occurs in humans, it may have implications for neurological symptoms associated with DA imbalances. Here we tested whether there are differences in the number of tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis) and DA transporter (DAT) immunoreactive neurons in the midbrain of people who died in summer (long-day photoperiod, n = 5) versus winter (short-day photoperiod, n = 5). TH and DAT immunoreactivity in neurons and their processes was qualitatively higher in summer compared with winter. The density of TH immunopositive (TH+) neurons was significantly (~6-fold) higher whereas the density of TH immunonegative (TH-) neurons was significantly (~2.5-fold) lower in summer compared with winter. The density of total neurons (TH+ and TH- combined) was not different. The density of DAT+ neurons was ~2-fold higher whereas the density of DAT- neurons was ~2-fold lower in summer compared with winter, although these differences were not statistically significant. In contrast, midbrain nuclear volume, the density of supposed glia (small TH- cells), and the amount of TUNEL staining were the same in summer compared with winter. This study provides the first evidence of an association between environmental stimuli (photoperiod) and the number of midbrain DA neurons in humans, and suggests DA neurotransmitter switching underlies this association.
Highlights
Changes in the brain or ‘brain plasticity’ underlie adaptive behavior and brain repair following injury or disease
D = depth = rostro-caudal. cNumber of counting sites is low due to a low volume of midbrain DA nuclei within the block provided. dRostro-caudal block location is not significantly different in summer compared with winter (p>0.05, unpaired, two-tailed t-test). eThe number of sections and number of counting sites are not significantly different in summer compared with winter (p>0.05, unpaired, two-tailed t-tests). fTH+ neuron density is ~6-fold higher and TH- neuron density is ~2.5-fold lower in summer compared with winter
780.6 738.2 872.2 1340.3 747.9 895.8 (113.6)e aNumber of counting sites is low due to a low volume of midbrain DA nuclei within the block provided. bThe number of sections and number of counting sites are not significantly different in summer compared with winter (p>0.05, unpaired, two-tailed t-tests). cAlthough DA transporter (DAT)+ neuron density is ~2-fold higher and DAT- neuron density is ~2-fold lower in summer compared with winter, these differences are not significantly different (p>0.017, unpaired, two-tailed t-tests with correction for multiple comparisons). dTotal neuron density (DAT+ & DAT- combined) is not significantly different (p>0.017, unpaired two-tailed t-test with correction for multiple comparisons) between summer and winter. eGlial cell density is not significantly different in summer compared with winter (p>0.05, unpaired, two-tailed t-tests)
Summary
Changes in the brain or ‘brain plasticity’ underlie adaptive behavior and brain repair following injury or disease. Adult rats exposed to less stressful short-day photoperiods have more hypothalamic dopamine (DA) neurons, whereas those exposed to more stressful long-day photoperiods have fewer hypothalamic DA neurons [1]. These changes are not associated with neurogenesis or apoptosis. Ablating hypothalamic DA neurons results in anxious and depressed behavior, and this is rescued by photoperiod-induction of more DA neurons [1]. Pairing male and female mice together continuously for 7 days results in more TH+ neurons in males (compared with male-male pairs) but fewer TH+ neurons in females (compared with female-female pairs) [3,4]. EE-induction of more midbrain TH+ neurons is abolished by concurrent local infusion of GABAA receptor antagonists, implicating afferent pathways, synaptic input and neuronal activity in mediating this effect [3,4]
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