title: Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice.
abstract: Neurological abnormalities, such as Parkinson-like disorders (PlD), are often co-morbidities of Type 2 Diabetic (T2D) patients, although the epidemiological link between these two disorders remains controversial. The PED/PEA-15 protein represents a possible candidate linking T2D and PD, because it is increased in subjects with T2D and is highly expressed in the brain. To test this hypothesis, we have analyzed the neurological and neurochemical phenotype of transgenic mice overexpressing PED/PEA-15 (tgPED). These mice develop impaired glucose tolerance and insulin resistance, accompanied by neurological features resembling PlD: feet clasping, slow and delayed locomotor movements in different behavioral tests in absence of clear cognitive deficits, ataxia or anxiety. Morphological analysis of the brains showed selective modifications of metabolic activity in the striatal region. In the same region, we have observed 26% decrease of dopamine fibers, confirmed by immunohistochemistry and Western Blot for tyrosine hydroxylase. Moreover, they also showed 48% reduction of dopamine levels in the striatum. Thus the tgPED mice may represent a genetic animal model of neurological disease linked to T2D.
authors.affiliation: URT- Genomica del Diabete, Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy.|Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perruolo
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.|Dept Medicine and Health Sciences, Univ. Molise, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Viggiano
authors.affiliation: URT- Genomica del Diabete, Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy.|Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fiory
authors.affiliation: URT- Genomica del Diabete, Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Cassese
authors.affiliation: URT- Genomica del Diabete, Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy.|Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nigro
authors.affiliation: URT- Genomica del Diabete, Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy.|Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Liotti
authors.affiliation: URT- Genomica del Diabete, Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy.|Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Miele
authors.affiliation: URT- Genomica del Diabete, Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy.|Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Beguinot
authors.affiliation: URT- Genomica del Diabete, Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy.|Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Formisano
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001522:Behavior, Animal; D004298:Dopamine / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008568:Memory; D008822:Mice, Transgenic; D009043:Motor Activity; D017072:Neostriatum / Q000378:metabolism; D010300:Parkinson Disease / Q000473:pathology*; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism; D045442:Rotarod Performance Test; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C490444:Pea15 protein, mouse; D010750:Phosphoproteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine