Related Experiment Videos
Regulation of rat brain vesicular monoamine transporter by chronic treatment with ovarian hormones
1Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Abstract:
Ovarian steroids play an important role in neuroregulation and in the pathophysiology of various neuropsychiatric disorders. Most of the studies focused on the impact of gonadal steroids on post-synaptic receptors and plasma membrane transporters. In the present study, we evaluated the effect of chronic treatment with ovarian steroids on the expression of rat brain vesicular monoamine transporter (VMAT2). Ovariectomized rats were treated for 21 days with estradiol, progesterone or both. VMAT2 gene expression was assessed on the protein level by high affinity [3H]dihydrotetrabenazine ([3H]TBZOH) binding using autoradiography and on the mRNA level by in situ hybridization. Progesterone administration led to a decrease in [3H]TBZOH binding in the middle striatum and in the nucleus accumbens and to a parallel decrease in VMAT2 mRNA level in the substantia nigra pars compacta and dorsal raphè nuclei. Chronic estradiol treatment reduced VMAT2 mRNA level in the dorsal raphè and [3H]TBZOH binding in middle part of the striatum and nucleus accumbens but did not affect VMAT2 mRNA level in the substantia nigra pars compacta. Simultaneous administration of both ovarian steroids did not modulate VMAT2 mRNA in the substantia nigra pars compacta as well as [3H]TBZOH binding in the striatum or the nucleus accumbens but reduced VMAT2 mRNA level in the dorsal raphè. It appears that ovarian steroids may play a crucial role in the regulation of VMAT2 gene expression in the dopamine and serotonin systems. This modulatory activity may be relevant to synaptic and neuronal plasticity as well as to the molecular and cellular pathophysiology of gender-specific neuropsychiatric disorders.
Insights
Ovarian steroids, like progesterone and estradiol, influence vesicular monoamine transporter 2 (VMAT2) gene expression in rat brains. This suggests a role in neuroregulation and gender-specific neuropsychiatric disorders.
Area of Science:
- Neuroendocrinology
- Molecular Psychiatry
- Neuropharmacology
Background:
- Ovarian steroids are crucial for neuroregulation and neuropsychiatric disorder pathophysiology.
- Previous research focused on gonadal steroid impact on post-synaptic receptors and plasma membrane transporters.
- The role of ovarian steroids in regulating vesicular monoamine transporter 2 (VMAT2) expression remains less understood.
Purpose of the Study:
- To investigate the effect of chronic estradiol and progesterone treatment on rat brain VMAT2 gene expression.
- To assess VMAT2 protein and mRNA levels following ovarian steroid administration.
Main Methods:
- Ovariectomized rats were treated with estradiol, progesterone, or both for 21 days.
- VMAT2 protein levels were measured using [3H]dihydrotetrabenazine ([3H]TBZOH) binding via autoradiography.
- VMAT2 mRNA levels were quantified using in situ hybridization.
Main Results:
- Progesterone decreased VMAT2 mRNA in the substantia nigra and dorsal raphe nuclei, and protein binding in the striatum and nucleus accumbens.
- Estradiol reduced VMAT2 mRNA in the dorsal raphe and protein binding in the striatum and nucleus accumbens.
- Combined treatment decreased VMAT2 mRNA in the dorsal raphe but did not affect striatal or nucleus accumbens binding.
Conclusions:
- Ovarian steroids significantly modulate VMAT2 gene expression in dopamine and serotonin systems.
- This regulation may impact synaptic plasticity and the pathophysiology of gender-specific neuropsychiatric disorders.
- Findings highlight a potential mechanism for ovarian steroid influence on monoamine neurotransmission.