title: l-DOPA reverses the impairment of Dentate Gyrus LTD in experimental parkinsonism via β-adrenergic receptors.
abstract: Parkinson's disease (PD) patients exhibit motor and non-motor symptoms that severely affect quality of life. Cognitive alterations in PD subjects have been related to both structural and functional hippocampal changes. Here we investigated the effects of the 6-hydroxydopamine (6-OHDA) lesion in the Medial Forebrain Bundle (MFB) on the hippocampus focusing on the Dentate Gyrus (DG). In vivo microdialysis measurements revealed that the 6-OHDA injection disrupts both dopaminergic and noradrenergic transmission in rat DG. In vitro electrophysiological recordings showed that these neurochemical alterations were accompanied by impairment of long-term depression (LTD) at medial perforant path/DG synapses. Furthermore, this alteration was reversed by l-DOPA treatment. Notably, the therapeutic effect of l-DOPA on LTD was blocked by the antagonism of β-noradrenergic receptors, but not by dopamine D1 or D2 receptor antagonists. Thus, while the dopaminergic transmission does not seem to be implicated in this therapeutic effect of l-DOPA, the noradrenergic system plays a central role in the synaptic dysfunction of the DG in experimental PD. Our work provides new evidence on the role of catecholamines in DG synaptic plasticity and sheds light on the possible synaptic mechanisms underlying cognitive deficits in PD. Furthermore, our results indicate that l-DOPA exerts a therapeutic effect on the parkinsonian brain through different, coexistent, mechanisms.
authors: Fondazione Santa Lucia, IRCCS, Rome, Italy.
authors: Valentina
authors: V
authors: Pendolino
authors: Fondazione Santa Lucia, IRCCS, Rome, Italy.
authors: Vincenza
authors: V
authors: Bagetta
authors: Fondazione Santa Lucia, IRCCS, Rome, Italy.
authors: Veronica
authors: V
authors: Ghiglieri
authors: Fondazione Santa Lucia, IRCCS, Rome, Italy.
authors: Carmelo
authors: C
authors: Sgobio
authors: Fondazione Santa Lucia, IRCCS, Rome, Italy.
authors: Emanuela
authors: E
authors: Morelli
authors: Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors: Silvia
authors: S
authors: Poggini
authors: Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors: Igor
authors: I
authors: Branchi
authors: Fondazione Santa Lucia, IRCCS, Rome, Italy; Dipartimento di Psicologia and Centro "Daniel Bovet", Sapienza - Università di Roma, Italy.
authors: Emanuele C
authors: EC
authors: Latagliata
authors: Fondazione Santa Lucia, IRCCS, Rome, Italy; Dipartimento di Psicologia and Centro "Daniel Bovet", Sapienza - Università di Roma, Italy.
authors: Tiziana
authors: T
authors: Pascucci
authors: Fondazione Santa Lucia, IRCCS, Rome, Italy; Dipartimento di Psicologia and Centro "Daniel Bovet", Sapienza - Università di Roma, Italy.
authors: Stefano
authors: S
authors: Puglisi-Allegra
authors: Fondazione Santa Lucia, IRCCS, Rome, Italy; Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy.
authors: Paolo
authors: P
authors: Calabresi
authors: Fondazione Santa Lucia, IRCCS, Rome, Italy. Electronic address: b.picconi@hsantalucia.it.
authors: Barbara
authors: B
authors: Picconi
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001552:Benzazepines / Q000494:pharmacology; D018891:Dentate Gyrus / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D007839:Functional Laterality; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use*; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D000978:Antiparkinson Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; C534628:SCH 23390; D007980:Levodopa; D013469:Sulpiride; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine
keywords: Dentate Gyrus; Long-term depression; Parkinson's disease; Synaptic plasticity; Whole-cell patch clamp recordings