Androgen receptors in Purkinje neurons are modulated by systemic testosterone and sexual training in a region-specific manner in the male rat

Pérez-Pouchoulén, Miguel; Toledo, Rebeca; Hernández, Luis García; Perez-Estudillo, Cesar A.; Coria-Ávila, Genaro A.; Hernández-Aguilar, María Elena; Carrillo, Porfirio; Manzo, Jorge

doi:10.1016/j.physbeh.2016.01.027

Cited by 24 publications

(23 citation statements)

References 56 publications

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“…Furthermore, the AR expression appeared to differ between the superficial and deep regions within the majority of cerebellar lobules in both sexes suggesting the location of AR‐expressing neurons in the Purkinje layer as an important anatomical factor regulating AR activity. This peculiar pattern expression of AR in Purkinje neurons resemblances the one observed in the adult cerebellum at least in male rats (Perez‐Pouchoulen et al, 2016). The AR has also been found in some, but not all, mature Purkinje neuron's dendrites (Perez‐Pouchoulen et al, 2016).…”

Section: Discussionsupporting

confidence: 78%

“…Subsequently, tissue was placed in 30% sucrose at 4 °C until they were saturated (approximately 72 h) before sectioning on a Leica cryostat. Forty micrometers sagittal sections were obtained from the mid‐vermis and processed for immunohistochemistry as described elsewhere (Perez‐Pouchoulen et al, 2016). Briefly, cerebellar sections were incubated with a polyclonal antibody against the AR (1:1500, rabbit anti‐AR, Santa Cruz Biotechnology sc‐816) in 0.4% PBS with Triton X‐100 (PBS‐T) for 48 h at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

“…We used 3 cerebellar sections from the mid‐vermis per animal, they were grouped and then averaged for each animal. This method has been used in our lab (Perez‐Pouchoulen et al, 2016) and with modifications by others (Finesmith and Favero, 2014; Hamson et al, 2009).…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, Purkinje neurons are known to express estrogen and progesterone receptors which both regulate neuroplasticity during cerebellar development (Haraguchi et al, 2012;Sakamoto et al, 2003Sakamoto et al, , 2001Sasahara et al, 2007;Tsutsui, 2008). Furthermore, the androgen receptor (AR) is also expressed by Purkinje neurons in the developing and adult cerebellum (Bowers et al, 2014;Perez-Pouchoulen et al, 2016;Qin et al, 2007), but its function in the neurobiology of the cerebellum remains unclear. In other brain regions, the AR regulates the expression of both cytoskeletal proteins such as tubulin (Jones and Oblinger, 1994;Matsumoto et al, 1994) and neurotrophic factors such as BDNF (brain-derived neurotrophic factor) (Yang et al, 2004) as it translocates to the cell nucleus functioning as a transcription factor (Chang et al, 1995;Lee and Chang, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Prenatal exposure to sodium valproate alters androgen receptor expression in the developing cerebellum in a region and age specific manner in male and female rats

Pérez-Pouchoulén

Miquel

Saft

et al. 2016

Intl J of Devlp Neuroscience

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Valproic acid (VPA) is an anti-epileptic drug with teratogenicity activity that has been related to autism. In rodents, exposure to VPA in utero leads to brain abnormalities similar than those reported in the autistic brain. Particularly, VPA reduces the number of Purkinje neurons in the rat cerebellum parallel to cerebellar abnormalities found in autism. Thus, we injected pregnant females on embryonic day 12 either with VPA (600mg/kg, i.p.) or 0.9% saline solution and obtained the cerebellum from their offspring at different postnatal time points. Testosterone has been linked to autism and plays an important role during brain development. Therefore, we identified and analyzed the androgen receptor (AR) by immunohistochemistry and densitometry, respectively. We found VPA decreases AR density in the superficial Purkinje layer only in cerebellar lobule 8 at PN7, but increased it at PN14 compared to control in males. In females, VPA decreased AR density in the superficial Purkinje layer in cerebellar lobule 6 at PN14, but increased it in lobule 9 at the same time point. No differences were found in the deep Purkinje layer of any cerebellar lobule in terms of AR density neither in males nor females. We additionally found a particular AR density decreasing in both superficial and deep regions across development in the majority of cerebellar lobules in males, but in all cerebellar lobules in females. Thus, our results indicate that VPA disrupts the AR ontogeny in the developing cerebellum in an age and region specific manner in male and female rats. Future epigenetic studies including the evaluation of histone deacetylases (HDAC's) might shed light these results as HDAC's are expressed by Purkinje neurons, interact with the AR and are VPA targets. This work contributes to the understanding of the cerebellar development and it might help to understand the role of the cerebellum in neurodevelopmental disorders such as autism.

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Section: Discussionsupporting

confidence: 78%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prenatal exposure to sodium valproate alters androgen receptor expression in the developing cerebellum in a region and age specific manner in male and female rats

Pérez-Pouchoulén

Miquel

Saft

et al. 2016

Intl J of Devlp Neuroscience

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“…ARs are highly expressed in the septum pellucidum, stria terminalis, preoptic area, ventromedial hypothalamus and cerebellum where they regulate the sexual reproductive behaviors [56,57]. Neuroandrogens production had detected in the hippocampus where they modulate the hippocampal structure specifically CA1 and CA3 areas.…”

Section: Androgen Actions In Normal Cognitionmentioning

confidence: 99%

Sex Hormones and Alzheimer’s Disease

Bahnasy¹,

El-Heneedy²,

El-Seidy³

2018

Sex Hormones in Neurodegenerative Processes and Diseases

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Alzheimer's disease (AD) is the most common type of dementia and the most common neurodegenerative disorder of elderly. It is not an accelerated form of aging but it is characterized by distinct temporospatial brain pathological changes, including amyloid plaques accumulation, neurofibrillary tangles deposition, synaptic loss and neuronal death with gross brain atrophy. These changes result in persistent progressive memory and cognitive decline interfering with the usual daily activities. AD is a multifactorial disorder results from the interaction of genetic, epigenetic, environmental and lifestyle factors. Estrogen, progesterone and androgen effects are important building stones in AD pathogenesis, and their effect in brain modulation and development results in different gender susceptibility to the disease. These sex hormones whether gonadal or neurosteroids (synthesized locally in the brain) play important neuroprotective roles influencing the individual's vulnerability to AD development, rate of mild cognitive impairment (MCI)/AD conversion and speed of AD progression. Despite the little therapeutic implications of hormonal replacement therapy in AD treatment, yet this topic still represents a challenging hopeful way to construct a strategy for the development of personalized, gender-specific AD management.

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Inhibition of androgenic pathway impairs encoding of cerebellar‐dependent motor learning in male rats

Panichi

Dieni

Sullivan

et al. 2022

J of Comparative Neurology

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Cerebellar-dependent learning is essential for the adaptation of motor and no motor behaviors to changing contexts, and neuroactive steroids-mainly referred to as estrogens-may regulate this process. However, the role of androgens in this process has not been established, although they may affect cerebellar physiology. Thus, this study aims to determine whether the activation of androgenic neural pathways may take part in controlling the vestibuloocular (VOR) and optokinetic reflexes (OKR), which depend on a defined cerebellar circuitry. To answer this question, we acutely blocked the activation of androgen receptors (Ars) using systemic administration of the Ars antagonist flutamide (FLUT; 20 mg/Kg) in peripubertal male rats. Then, we evaluated the FLUT effect on general oculomotor performance in the VOR and OKR as well as VOR adaptive gain increases and decreases. We used a paradigm causing fast VOR adaptation that combined in phase/out phase visuo-vestibular stimulations. We found that FLUT impaired the gain increase and decrease in VOR adaptation. However, FLUT altered neither acute nor overtime basal ocular-motor performance in the VOR or OKR. These findings indicate that the activation of androgenic neural pathways participates in phenomena leading to fast VOR adaptation, probably through the modulation of plasticity mechanisms that underlie adaptation of this reflex. Conversely, androgens may not be essential for neural information processing demands in basal ocular-motor reflexes. Moreover, our results suggest that androgens, possibly testosterone and dihydrotestosterone, could rapidly regulate motor memory encoding in the VOR adaptation, acting at both cerebellar and extracerebellar plasticity sites.

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Androgen receptors in Purkinje neurons are modulated by systemic testosterone and sexual training in a region-specific manner in the male rat

Cited by 24 publications

References 56 publications

Prenatal exposure to sodium valproate alters androgen receptor expression in the developing cerebellum in a region and age specific manner in male and female rats

Prenatal exposure to sodium valproate alters androgen receptor expression in the developing cerebellum in a region and age specific manner in male and female rats

Sex Hormones and Alzheimer’s Disease

Inhibition of androgenic pathway impairs encoding of cerebellar‐dependent motor learning in male rats

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