Mendell AI, Atwi S, Bailey CD, McCloskey DP, Scharfman HE, MacLusky NJ (2017) Expansion of mossy fibers and CA3 apical dendritic length accompanies the fall in dendritic spine density after gonadectomy in male, but not female, rats. Brain Struct Funct. 2222:587-601.

This paper follows a physiological study of gonadectomized rats that showed surprising expansion of mossy fibers and increased mossy fiber synaptic responses after gonadectomy in males (Skucas et al, 2013, see below). The Golgi staining described in the present study showed that the expansion of mossy fibers is also robust by Golgi staining and consistent with the physiology. In addition, gonadectomized females did not show these changes.

Yang J, Harte-Hargrove LC, Siao CJ, Marinic T, Clarke R, Ma Q, Jing D, Lafrancois JJ, Bath KG, Mark W, Ballon D, Lee FS, Scharfman HE, Hempstead BL. (2014) proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus.  Cell Rep. 7:796-806.

Scharfman HE, MacLusky NJ (2013) Differentiation regulation of BDNF, synaptic plasticity and mossy fiber sprouting in the hippocampal mossy fiber pathway of male and female rats. Neuropharmacology. Special issue: BDNF Regulartion of Synaptic Structure, Function and Plasticity, CM Bramham, D Panja, Eds.

Skucas VA, Duffy AM, Harte-Hargrove LC, Magagna-Poveda A, Radman T, Chakraborty G, Schroeder CE, MacLusky NJ, Scharfman HE (2013) Testosterone depletion in adult male rats increases mossy fiber transmission, LTP, and sprouting in area CA3 of hippocampus. J. Neurosci. 33: 2338-2355.

This study showed that gonadectomized male rats exhibited increased BDNF expression in the mossy fiber axons of hippocampus.  Mossy fiber transmission was increased in a manner consistent with a new BDNF-dependence.  Mossy fiber LTP was also increased and exhibited dependence on trkB receptors, which bind BDNF.  The mossy fiber axons exhibited sprouting into stratum oriens, and current source density analysis suggested that new synapses were made by sprouted axons. The remarkable increase in plasticity in gonadectomized male rats suggests that testosterone may normally suppress excitability and plasticity, which could be advantageous to prevent seizures and excitotoxicity, but at the ‘price’ of reduced plasticity.


Skucasetal2013JNeurosci GdxCA3 final.pdf

Special issue of Neuroscience (2012): Steroid hormones in the CNS: The role of BDNF. Guest Editors: Scharfman HE, Kramar EA, Luine VN, Srivastava D.

McNamara JO, Scharfman HE (2012) Temporal lobe epilepsy and the BDNF receptor, TrkB. In: Jasper’s Basic Mechanisms of the Epilepsies. Fourth Edition. Eds: Noebels JN, Avoli M, Rogawski MA, Olsen R, Delgado-Escueta A. Bethesda, MD: Natl. Ctr. for Biotech. Information.

Harte-Hargrove LC, MacLusky NJ, Scharfman HE (2012) Brain-derived neurotrophic factor-estrogen interactions in the hippocampal mossy fiber pathway: Implications for normal brain function and disease. Neuroscience.

Skucas VA, Mathews B, Yang J, Cheng Q, Triester A, Dffy AM, Verkman AS, Hempstead BL, Wood MA, Binder DK, Scharfman HE (2011) Impairment of select forms of spatial memory and neurotrophin-dependent synaptic plasticity by deletion of glial aquaporin-4. J Neurosci. 31:6392-6396.

This study showed that deletion of the major type of water channel in the brain, aquaporin-4 (AQP4) impaired the BDNF-dependent form of LTP that is induced by simulating theta rhythm.  It also reduced performance on a task that is used to assess spatial memory. This is the first demonstration that a water channel affects synaptic plasticity and behavior.

Chakraborty G, Magagna-Poveda A, Parratt C, Umans JG, MacLusky NJ, Scharfman HE (2012)Reduced hippocampal brain-derived neurotrophic factor (BDNF) in neonatal rats after prenatal exposure to propylthiouracil (PTU). Endocrinology 153:1311-6.

This study showed that prenatal exposure of female rats to an agent that reduces thyroid hormone leads to a decrease in BDNF protein in the hippocampus of newborn rat pups. In previous studies that looked at older offspring the effect was not found, suggesting a transient effect that might impact developing pups. The decrease in thyroid hormone was low, suggesting relevance to subclinical maternal hypothyroidism, which can occur in response to many conditions. Therefore, the results suggest a potential mechanism linking mild prenatal effects to deleterious neurodevelopment in offspring.

Scharfman HE (2009) The role of BDNF in epileptogenesis and epilepsy. In: The Enyclopedia of Epilepsy Research. Ed: Schwartzkroin, PA. New York: Elsevier.

This review discusses the role of the neurotrophin BDNF in epilepsy.



Scharfman HE, MacLusky NJ (2008) Estrogen-growth factor interactions and their contribution to neurological disorders. Headache 48: S2 77-89.

This article reviews the evidence that BDNF contributers to the actions of estrogen. The emphasis is on neurological disorders such as epilepsy and migraine.


MacBeth AH, Scharfman HE, MacLusky NJ, Luine VN (2008) Effects of multiparity on recognition memory, monoaminergic neurotransmitters, and brain-derived neurotrophic factor (BDNF). Horm Beh., 76: 36-44.


Scharfman HE, Hintz TM, Gomez J, Stormes KA, Barouk S, Malthanakar--Phatak GH, McCloskey DP, Luine VN, MacLusky NJ (2007) Changes in hippocampal fuction in ovariectomized rats after sequential low doses of estradiol to simulate the preovulatory estrogen surge. Eur J Neurosci.  26: 2595-2612.

This study showed that the effects of the estrous cycle in the female rat (J. Neurosci. 2003) could be explained by the rise in estradiol levels during the estrous cycle., and that BDNF played an important role.  It also provides the methods for a protocol that can be used in female rats to simulate the serum levels of estradiol during the preovulatory surge. 


Scharfman HE, MacLusky NJ (2006) Estrogen and BDNF: complexity of steroid hormone-growth factor interactions. Front. Neuroendocrin. 27:415-435.

This review addresses the actions of estrogen that are potentially mediated by BDNF and neuropeptide Y (NPY).


Scharfman HE (2005) BDNF and the dentate gyrus mossy fibers: Implications for epilepsy.  In: Synaptic plasticity and transynaptic signaling Eds: Stanton PK, Bramham CR, Scharfman HE. New York: Springer Science and Business Media.

This article provides an overview of the studies in the Scharfman laboratory that support the hypothesis that BDNF is ‘proconvulsant.’  This review was published in a book dedicated to Dr. John Sarvey, based on a meeting held to honor his valued contributions as a scientist, colleague, and mentor.




Scharfman HE, MacLusky NJ (2005) Similarities between BDNF and estrogen: coincidence or clue? Trends Neurosci. 28: 79-85.

This article discusses the uncanny similarities between actions of estrogen and BDNF, with an emphasis on hippocampus. Our hypothesis is that many of the actions of estrogen are mediated by BDNF, and that explains the similarities.



Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth factors.22: 123-131.

This review explains what BDNF is, its main receptors and signalling mechanisms, and many of the ways it contributes to normal development and normal function in the adult brain.



Scharfman HE et al (2003) Hippocampal excitability changes across the estrous cycle in the rat: a potential role for BDNF. J Neurosci. 23:11641-11652.

This paper showed that female rats have a cyclical increase in mossy fiber excitability and mossy fiber BDNF expression that follows the preovulatory estrogen surge.  The physiological changes in mossy fiber transmission were blocked by an antagonist of trk receptors, implicating BDNF mechanistically.



Scharfman HE et al (2002) Spontaneous recurrent seizures after intrahippocampal infusion of brain-derived neurotrophic factor (BDNF). Exp Neurol. 174: 201-214.

Using normal adult male rats, this study showed that infusion of recombinant BDNF by an osmotic pump with a cannula in the hippocampus produced spontaneous seizures in approximately 1/3 of the animals, but vehicle did not have a detectable effect.  The results support the hypothesis that BDNF is “proconvulsant.”



Binder DK, Gall CM. Croll SD, Scharfman HE (2001) BDNF and epilepsy: too much of a good thing? Trends in Neurosci. 24: 47-53.

This review was written by participants in a symposium about BDNF and epilepsy at the American Epilepsy Society annual meeting in 2000.  It suggests that actions of BDNF can be protective and be important to the normal function of the CNS, but under some conditions BDNF increases the susceptibility to seizures and epilepsy.  Therefore, it has “good” effects but also “bad” effects.  It also proposes that BDNF contributes to epileptogenesis, the transformation of a normal brain into one that has spontaneous recurrent seizures.  One of the ways it may do so is by a positive feedback mechanism where BDNF levels are increased after events that initiate epileptogenesis.  In this context, the focus is on Temporal Lobe Epilepsy (TLE), which is only one type of epilepsy, but is most relevant because patients often develop TLE after a precipitating event that increases BDNF levels in the temporal lobe and areas connected to it.



Croll SD, Suri C, Compton DL, Simmons MV, Yancopoulos GD, Lindsay RM, Wiegand SJ, Rudge JS, Scharfman HE (1999)  Brain-derived neurotrophic factor transgenic mice exhibit passive avoidance deficits, increased seizure severity and in vitro hyperexcitability in the hippocampus and entorhinal cortex.  Neuroscience 93:1491-1506.

This paper described the phenotype of BDNF overexpressing mice.  Animals had learning deficits in vivo and LTP deficits in vitro.  One of the reasons for the deficits in vitro was suggested to be spreading depression episodes evoked by LTP-inducing stimuli.



Scharfman HE, Goodman JH, Sollas AL (1999)  Actions of brain-derived neurotrophic factor in slices from rats with spontaneous seizures and mossy fiber sprouting in the dentate gyrus. J Neurosci. 19: 5619-5631.

This paper demonstrated that slices from epileptic rats exhibit spontaneous epileptiform discharges of granule cells in the dentate gyrus when exposed to recombinant BDNF. In addition, BDNF was expressed in the sprouted axons of dentate gyrus granule cells, implicating BDNF in the abnormal network excitablity in the dentate gyrus of epileptic animals.



Scharfman HE (1997) Hyperexcitability in combined entorhinal/hippocampal slices of adult rat after exposure to brain-derived neurotrophic factor. J Neurophysiol  78: 1082-1095.

This study showed that BDNF application to hippocampal slices induced potentiation of the mossy fiber pathway that was homosynaptic.  Effects were compared to low doses of kainic acid and could evoke spreading depression episodes.  This paper suggested for the first time that mossy fiber BDNF may be important to plasticity in area CA3 but also contribute - and potentially explain - the susceptibility of the hippocampus to seizures.



If you can not download a file or have any questions please contact Helen Scharfman at or