We reported previously that striatal excitotoxic lesion with quinolinic acid of rat pups during the first 2 weeks of postnatal life results in loss of dopaminergic neurons of the substantia nigra (SN) due to induced apoptosis. Here we demonstrate by immunohistochemistry that, following such a lesion, high levels of cyclin-dependent kinase 5 (cdk5) protein are present exclusively in apoptotic ce...

While deregulation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neurodegenerative diseases, its precise role in synaptic plasticity and memory remains elusive. Proteolytic cleavage of p35, a regulatory subunit of Cdk5, by calpain results in the generation of the truncated p25 protein, which causes hyperactivation of Cdk5. Using region-specific and inducible transgenic mice, we sho...

Cyclin-dependent kinase (Cdk) 5 reduces the rewarding properties of psychostimulants by dampening postsynaptic dopamine (DA) receptor signaling. Cdk5 is also present in midbrain DA neurons, where the DA transporter (DAT) is localized and limits DA neurotransmission by removing extracellular DA. Here, we tested the hypothesis that Cdk5 could also affect the disposition of DA by regulating DAT ac...

Cell cycle progression is tightly controlled by the activity of cyclin-dependent kinases (CDKs) [31]. CDKs are inactive as monomers, and activation requires binding to cyclins, a diverse family of proteins whose levels oscillate during the cell cycle, and phosphorylation by CDK-activating kinase (CAK) on a specific threonine residue [19]. In addition to the positive regulatory role of cyclins a...

Cyclin-dependent kinase 5 (Cdk5) is much more than its name implies; it plays a role in neuronal migration, neurite outgrowth and degeneration. Recent evidence suggests that Cdk5 regulates neuronal adhesion and cytoskeletal dynamics.

Polymorphisms in the Synapsin III (Syn III) gene can associate with attention deficits and hyperactivity disorder (ADHD), a neurodevelopmental characterized by alterations mesocorticolimbic nigrostriatal dopaminergic pathways. In spite of evidence supporting that Syn controls development cortical hippocampal short-projecting neurons, whether it plays similar role midbrain neurons (mDN), owning ...

CDK5 is a member of the cyclin-dependent kinase family with diverse functions in both the developing and mature nervous system. The inappropriate activation of CDK5 due to the proteolytic release of the activator fragment p25 from the membrane contributes to the formation of neurofibrillary tangles and chronic neurodegeneration. At 18 months of age 3xTg-AD mice were sacrificed after 1 year (lon...

Neuronal loss occurs in several neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, as well as following acute insults, such as brain ischemia and trauma. In general, cell death can be categorized into two main types, apoptosis and necrosis, which are differentiated by distinct morphological and biochemical features. Cell death of neurons possesses special characte...

The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that regulates cell cycle progression in proliferating cells. To enter the S-phase, APC/C must be inactivated by phosphorylation of its cofactor, Cdh1. In post-mitotic cells such as neurons APC/C-Cdh1 complex is highly active and responsible for the continuous degradation of mitotic cyclins. However, the specific molecul...

Dopamine and cAMP-regulated phosphoprotein of M(r) 32,000 (DARPP-32) plays an obligatory role in most of the actions of dopamine. In resting neostriatal slices, cyclin-dependent kinase 5 (Cdk5) phosphorylates DARPP-32 at Thr-75, thereby reducing the efficacy of dopaminergic signaling. We report here that dopamine, in slices, and acute cocaine, in whole animals, decreases the state of phosphoryl...