TY - JOUR
T1 - Neuroplasticity and inflammatory alterations in the nucleus accumbens are corrected after risperidone treatment in a schizophrenia-related developmental model in rats
AU - Tendilla-Beltrán, Hiram
AU - Coatl-Cuaya, Heriberto
AU - Meneses-Prado, Silvia
AU - Vázquez-Roque, Ruben Antonio
AU - Brambila, Eduardo
AU - Tapia-Rodríguez, Miguel
AU - Martín-Hernández, David
AU - Garcés-Ramírez, Linda
AU - Madrigal, José L.M.
AU - Leza, Juan C.
AU - Flores, Gonzalo
N1 - Publisher Copyright:
© 2021
PY - 2021/9
Y1 - 2021/9
N2 - Increased dopaminergic activity in the striatum underlies the neurobiology of psychotic symptoms in schizophrenia (SZ). Beyond the impaired connectivity among the limbic system, the excess of dopamine could lead to inflammation and oxidative/nitrosative stress. It has been suggested that atypical antipsychotic drugs attenuate psychosis not only due to their modulatory activity on the dopaminergic/serotonergic neurotransmission but also due to their anti-inflammatory/antioxidant effects. In such a manner, we assessed the effects of the atypical antipsychotic risperidone (RISP) on the structural neuroplasticity and biochemistry of the striatum in adult rats with neonatal ventral hippocampus lesion (NVHL), which is a developmental SZ-related model. RISP administration (0.25 mg/kg, i.p.) ameliorated the neuronal atrophy and the impairments in the morphology of the dendritic spines in the spiny projection neurons (SPNs) of the ventral striatum (nucleus accumbens: NAcc) in the NVHL rats. Also, RISP treatment normalized the pro-inflammatory pathways and induced the antioxidant activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in this model. Our results point to the neurotrophic, anti-inflammatory, and antioxidant effects of RISP, together with its canonical antipsychotic mechanism, to enhance striatum function in animals with NVHL.
AB - Increased dopaminergic activity in the striatum underlies the neurobiology of psychotic symptoms in schizophrenia (SZ). Beyond the impaired connectivity among the limbic system, the excess of dopamine could lead to inflammation and oxidative/nitrosative stress. It has been suggested that atypical antipsychotic drugs attenuate psychosis not only due to their modulatory activity on the dopaminergic/serotonergic neurotransmission but also due to their anti-inflammatory/antioxidant effects. In such a manner, we assessed the effects of the atypical antipsychotic risperidone (RISP) on the structural neuroplasticity and biochemistry of the striatum in adult rats with neonatal ventral hippocampus lesion (NVHL), which is a developmental SZ-related model. RISP administration (0.25 mg/kg, i.p.) ameliorated the neuronal atrophy and the impairments in the morphology of the dendritic spines in the spiny projection neurons (SPNs) of the ventral striatum (nucleus accumbens: NAcc) in the NVHL rats. Also, RISP treatment normalized the pro-inflammatory pathways and induced the antioxidant activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in this model. Our results point to the neurotrophic, anti-inflammatory, and antioxidant effects of RISP, together with its canonical antipsychotic mechanism, to enhance striatum function in animals with NVHL.
KW - Atypical antipsychotics
KW - MAP kinases
KW - Nrf2
KW - Smad
KW - Spiny projection neurons
KW - Stereology
UR - http://www.scopus.com/inward/record.url?scp=85110640544&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2021.07.014
DO - 10.1016/j.schres.2021.07.014
M3 - Artículo
C2 - 34298239
AN - SCOPUS:85110640544
SN - 0920-9964
VL - 235
SP - 17
EP - 28
JO - Schizophrenia Research
JF - Schizophrenia Research
ER -
