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Rapid Golgi Stain for Dendritic Spine Visualization in Hippocampus and Prefrontal Cortex
Published on: December 3, 2021
Increased dendritic spine density and tau expression are associated with individual differences in steroidal
Pranay Bharadwaj1, Christine McInnis, Amanda M K Madden
1Psychology Department, University of Massachusetts, Boston, Boston, Massachusetts, United States of America.
Abstract:
Male sexual behavior (MSB) is modulated by gonadal steroids, yet this relationship is highly variable across species and between individuals. A significant percentage (~30%) of B6D2F1 hybrid male mice demonstrate MSB after long-term orchidectomy (herein after referred to as "maters"), providing an opportunity to examine the mechanisms that underlie individual differences in steroidal regulation of MSB. Use of gene expression arrays comparing maters and non-maters has provided a first pass look at the genetic underpinnings of steroid-independent MSB. Surprisingly, of the ~500 genes in the medial preoptic area (MPOA) that differed between maters and non-maters, no steroid hormone or receptor genes were differentially expressed between the two groups. Interestingly, best known for their association with Alzheimer's disease, amyloid precursor protein (APP) and the microtubule-associated protein tau (MAPT) were elevated in maters. Increased levels of their protein products (APP and tau) in their non-pathological states have been implicated in cell survival, neuroprotection, and supporting synaptic integrity. Here we tested transgenic mice that overexpress tau and found facilitated mounting and intromission behavior after long-term orchidectomy relative to littermate controls. In addition, levels of synaptophysin and spinophilin, proteins generally enriched in synapses and dendritic spines respectively, were elevated in the MPOA of maters. Dendritic morphology was also assessed in Golgi-impregnated brains of orchidectomized B6D2F1 males, and hybrid maters exhibited greater dendritic spine density in MPOA neurons. In sum, we show for the first time that retention of MSB in the absence of steroids is correlated with morphological differences in neurons.
Insights
Male sexual behavior (MSB) persists in some mice after castration, linked to elevated brain proteins like tau and increased neuronal spine density in the medial preoptic area (MPOA). This suggests structural brain changes support steroid-independent sexual function.
Area of Science:
- Neuroendocrinology
- Behavioral Neuroscience
- Molecular Biology
Background:
- Male sexual behavior (MSB) is typically regulated by gonadal steroids, but individual variability exists.
- A subset of male mice (~30%) maintain MSB after long-term orchidectomy (maters), offering a model to study steroid-independent mechanisms.
- Previous studies identified differential gene expression in the medial preoptic area (MPOA) between maters and non-maters.
Purpose of the Study:
- To investigate the molecular and morphological underpinnings of steroid-independent male sexual behavior (MSB).
- To explore the role of specific genes and proteins, including amyloid precursor protein (APP) and tau (MAPT), in maintaining MSB without gonadal steroids.
- To examine neuronal morphology and synaptic protein levels in the MPOA of mice exhibiting persistent MSB.
Main Methods:
- Gene expression arrays were used to compare the MPOA of maters and non-maters.
- Levels of APP and MAPT were assessed, and transgenic mice overexpressing tau were tested for MSB.
- Synaptophysin and spinophilin levels were measured, and dendritic morphology was analyzed in Golgi-impregnated MPOA neurons.
Main Results:
- No steroid hormone or receptor genes were differentially expressed between maters and non-maters.
- Amyloid precursor protein (APP) and microtubule-associated protein tau (MAPT) were elevated in maters.
- Overexpression of tau facilitated MSB post-orchidectomy; maters showed increased synaptophysin, spinophilin, and dendritic spine density in MPOA neurons.
Conclusions:
- Steroid-independent MSB retention is associated with elevated levels of APP and tau in the MPOA.
- Increased synaptic protein levels and enhanced dendritic spine density in MPOA neurons correlate with persistent MSB.
- Neuronal morphological differences, rather than altered steroid receptor expression, may underlie individual variations in MSB regulation.
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