Daniela Parolaro
Daniela Parolaro
affiliation: Università dell'Insubria
research area(s): Neuroscience, Developmental Biology
Course: Neurobiology
University/Istitution: Università dell'Insubria
Daniela Parolaro was appointed in 2000 Full Professor of Cellular and Molecular Pharmacology at the Faculty of Sciences of Insubria University. She began her research activity at the Department of Pharmacology of the University of Milan (1972-2000), and then at the PsychoPharmacology Section of DBSF of the Insubria University (2000-until now). Her research is mainly concerned with receptor activation mechanisms and transduction pathways alterations upon drugs exposure. Recently her interest was focused on the long lasting consequrences of drug abuse in adolescence with particular attention to depression and psychotic like behavior.She has published more than 110 papers, particularly on drugs of abuse, in international qualified journals and has been invited as speaker in numerous national and
international conferences. She is member of the Italian Society of Pharmacology, Italian Society of Neuropsychopharmacology, Italian Society of Neuroscience,International Cannabinoid Research Society. In 2005 she is President-elect of the International Cannabinoid Research Society. Member of the executive board of the IACM (International Association for Cannabis as Medicine). Member of the scientific committee of the Center of Behavioral Pharmacology and Dependence,University of Milan;
Since 2002 until 2008 she acts as President of the Center of Neuroscience, University of Insubria and now she is member of the scientific
committee. She holds the position of Director of the Degree in Medical Biology at the Faculty of Sciences of Insubria University. From 2005 until now, she acts as Coordinator of the PhD in Neurobiology at the University of Insubria
Her research is mainly concerned with receptor activation mechanisms and transduction pathways alterations upon drugs exposure. She begun working in the cannabinoid field in 1994 publishing on cannabinoid/opioid interaction at the CNS level. Her current research is mainly concerned with the cellular effects of in vivo chronic administration of natural and synthetic cannabinoids in the CNS. Besides the demonstration of the occurrence of behavioral tolerance and physical dependence to natural, synthetic and endogenous cannabinoids, she focused her attention on the cellular mechanisms underlying these phenomena, showing the relevance in specific brain areas of the alterations in receptor number and efficiency, and cyclic AMP cascade. Her current research is focused on the long-term consequences of adolescent exposure to cannabinoids, exploring alterations in behavioural responses (emotional behavior, cognition and psychotic symptoms) and their cellular correlates (CB1 receptor level and G protein coupling, CREB activation, markers of neuroplasticity). Recently, she focused her attention on a more clinically relevant topic, that is to clarify the possible role that the (endo)cannabinoid system plays in the neurobiology of anxiety, depression and schizophrenia, maintaining the peculiarity of coupling behavioural responses with their cellular correlates. Finally, she is also exploring the effect of cannabidiol, a non-psychoactive component of cannabis sativa, demonstrating its ability to inhibits glioma cell proliferation either in vitro as in vivo. The mechanism of this action lies on the activation of caspases pathway with concomitant inhibition of 5-LOX pathway. Studies are now in progress to evaluate whether Cannabidiol possesses antiangiogenetic activity through morphological (endothelial cell tube formation, wounding test) and biochemical approaches
Chronic Blockade of CB1 Receptors Reverses Startle Gating Deficits and Associated Neurochemical Alterations in Isolation Reared Rats.
Zamberletti E, Piscitelli F, Cadeddu F, Rubino T, Fratta W, Fadda P, Di Marzo V, Parolaro D.
Br J Pharmacol. 2012 Jul 4. doi: 10.1111/j.1476-5381.2012.02095.x. [Epub ahead of print]

The endocannabinoid system and schizophrenia: integration of evidence.
Zamberletti E, Rubino T, Parolaro D.Curr Pharm Des. 2012 Jun 7. [Epub ahead of prinPMID22716159[PubMed - as supplied by publisher]
Solinas M, Massi P, Cantelmo A, Cattaneo M, Cammarota R, Bartolini D, Cinquina V, Valenti M, Vicentini L, Noonan D, Albini A, Parolaro D.
Br J Pharmacol. 2012 May 25. doi: 10.1111/j.1476-5381.2012.02050.x. [Epub ahead of print]

Massi P, Solinas M, Cinquina V, Parolaro D.
Br J Clin Pharmacol. 2012 Apr 17. doi: 10.1111/j.1365-2125.2012.04298.x. [Epub ahead of print]
[PubMed - as supplied by publisher]

Sala M, Braida D, Lentini D, Busnelli M, Bulgheroni E, Capurro V, Finardi A, Donzelli A, Pattini L, Rubino T, Parolaro D, Nishimori K, Parenti M, Chini B.
Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: a neurobehavioral model of autism.
Biol Psychiatry. 2011 May 1;69(9):875-82.

Bolognini D, Cascio MG, Parolaro D, Pertwee RG.AM630 behaves as a protean ligand at the human cannabinoid CB(2) receptor.
Br J Pharmacol. 2011 May 26. doi: 10.1111/j.1476-5381.2011.01503.x.

Zamberletti E, Viganò D, Guidali C, Rubino T, Parolaro D.Long-lasting recovery of psychotic-like symptoms in isolation-reared rats after chronic but not acute treatment with the cannabinoid antagonist AM251 Int J Neuropsychopharmacol. 2010 Oct 6:1-14.

Realini N, Vigano' D, Guidali C, Zamberletti E, Rubino T, Parolaro D.IChronic URB597 treatment at adulthood reverted most depressive-like symptoms induced by adolescent exposure to THC in female rats.
Neuropharmacology. 2011 Feb-Mar;60(2-3):235-43.

Parolaro D, Realini N, Vigano D, Guidali C, Rubino T.
The endocannabinoid system and psychiatric disorders.
Exp Neurol. 2010 Jul;224(1):3-14.

Guidali C, Viganò D, Petrosino S, Zamberletti E, Realini N, Binelli G, Rubino T, Di Marzo V, Parolaro D.Cannabinoid CB1 receptor antagonism prevents neurochemical and behavioural deficits induced by chronic phencyclidine.
Int J Neuropsychopharmacol. 2011 Feb;14(1):17-28

Parolaro D, Rubino T, Viganò D, Massi P, Guidali C, Realini N Cellular mechanisms underlying the interaction between cannabinoid and opioid system.
Curr Drug Targets. 2010 Apr;11(4):393-405

Bolognini D, Costa B, Maione S, Comelli F, Marini P, Di Marzo V, Parolaro D, Ross RA, Gauson LA, Cascio MG, Pertwee RG.The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. Br J Pharmacol. 2010 Jun;160(3):677-87

Realini N, Rubino T, Parolaro D. Neurobiological alterations at adult age triggered by adolescent exposure to cannabinoids.
Pharmacol Res. 2009 Aug;60(2):132-8.

Braida D, Capurro V, Zani A, Rubino T, Viganò D, Parolaro D, Sala M Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents.Br J Pharmacol. 2009 Jul;157(5):844-53.

Rubino T, Realini N, Braida D, Alberio T, Capurro V, Viganò D, Guidali C, Sala M, Fasano M, Parolaro D.
The depressive phenotype induced in adult female rats by adolescent exposure to THC is associated with cognitive impairment and altered neuroplasticity in the prefrontal cortex.
Neurotox Res. 2009 May;15(4):291-302

Rubino T, Realini N, Braida D, Guidi S, Capurro V, Viganò D, Guidali C, Pinter M, Sala M, Bartesaghi R, Parolaro D.
Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood.
Hippocampus. 2009 Aug;19(8):763-72

Project Title:
Drug abuse in adolescence as a risk factor for psychiatric diseases: an experimental approach
Despite the increasing use substances among adolescents, there are little and often contradictory studies on the long-term neurobiological consequences of drug abuse in juveniles. Adolescence is a critical phase for cerebral development, where the endocannabinoid system plays an important role influencing the release and action of different neurotransmitters. Therefore, a strong stimulation by the psychoactive drugs, might lead to subtle but lasting neurobiological changes that can affect adult brain functions and behavior.Our previous research aimed to investigate whether cannabis
exposure during adolescence can induce neurobiological modifications responsible for an increased vulnerability to psychiatric disorders and drug abuse in adulthood. Moreover, a possible difference between males and females was evaluated. On these bases, male and female rats were treated with increasing doses of THC from post natal day (PND) 35 to 45 and, an integrative study including behavioral, neurochemical, morphological, electrophysiological and proteomic approaches was carried out in adulthood (from PND 75).This approach allows us to demonstrate the presence of a depressive like phenotype in our females rats pre exposed to THC in adolescence coupled with impairment in recognition and spatial memories together with reduced synaptic plasticity in the prefrontal cortex. In contrast male rats only exhibited spatial memory impairment and reduced arborisation of dendritic tree in the hippocampus. The depressive phenotype present in females was antagonized by the treatment with indirect agonist of the endocannabinoid system strongly supporting the idea that reduced functionality of the endocannabinoid system can be considered one of the molecular underpinning of the observed phenotype . Recently we showed that when rats were tested for their sensitivity to psychostimulants , adult animals pre exposed to THC in adolescence were sensitized to the motor effect of phencyclidine thus suggesting the presence of a more complex phenotype resembling schizophrenia or a schizoaffective disorder.
Now our aim is the following.
- clarify the cellular events involved in the schizoaffective phenotype induced by THC in adolescence focusing the attention on a specific cerebral region such as the prefrontal cortex. In this area we will characterize the GABAergic and the Glutamatergic system through biochemical ( binding and signalling studies) and electrophysiological studies ( Microdialysis approache). To validate some results SiRNA approach will applied.
- verify whether abuse in adolescence of other drugs such as nandrolone and ecstasy produce long lasting effect on brain and behaviour once again exploring the molecular underpinning of the observed phenotype
-in presence of depression /psychotic behavior due to the abuse of nandrolone or ecstasy, test the effect of the treatment with direct/indirect modulator of the endocannabinoid system on the observed phenotypes

Project Title:
Phytocannabinoids and glioma
Our recent data showed that Cannabidiol ( CBD) a non psychoactive compound present in cannabis plant, possesses antiproliferative and antiinvasive effect in vitro against different lines of glioma cells with a mechanism not involving cannabinoid receptors
Moreover CBD exhibits antiangiogenic effect in vitro as well as in “ex vivo” approaches. However the mechanism of action of this compound remains to be elucidated and our preliminary data seem suggest the presence of a multitarget effect involving inhibition of pERK , AkT and HIF1alfa together with the production of oxygen radicals.
Our project will be focused on the further elucidation of the cellular pathways modified by CBD with particular attention to Id1 transcription factor ant its relation with the above mentioned pathways.
Additionally the efficacy on glioma cell of other non psychoactive phytocannabinoids ( cannbigerol, cannabdivarine ) and their mechanism of action will be explored.