all Michael E. Greenberg stories

Middle Eastern families yield intriguing clues to autism

404132862 — Fri, 11 Jul 2008 12:27:58 -0400

Research involving large Middle Eastern families, sophisticated genetic analysis and groundbreaking neuroscience has implicated a half-dozen new genes in autism. More importantly, it strongly supports the emerging idea that autism stems from disruptions in the brain’s ability to form new connections in response to experience – consistent with autism’s onset during the first year of life, when many of these connections are normally made.

Harvard researchers selected for National Academy of Sciences membership

yvette — Tue, 29 Apr 2008 16:39:20 -0400

Eight Harvard faculty members this week were elected to membership in the National Academy of Sciences in recognition of their distinguished and continuing achievements in original research.

Protein underlies brain's response to activity

70652986 — Mon, 26 Mar 2007 06:25:00 -0400

Experience helps shape the brain, but how that happens - how synapses are remodeled in response to activity - is one of neurobiology's biggest mysteries. Though axons and dendrites can be easily spotted waxing and waning under the microscope, the molecular middlemen working inside the cell to shape the neuron's sinewy processes have been much more elusive.

Two independent teams of Harvard Medical School (HMS) researchers report that they have found a protein that either pares down or promotes a neuron's synapses, depending on whether or not the neuron is being activated. Rather than work at the far reaches of the cell, in the axon or dendrite, the protein myocyte enhancer factor 2 (MEF2) resides in the nucleus, where it turns on and off genes that control dendritic remodeling. In fact, the researchers have identified some of MEF2's targets. In addition, one of the teams has identified how MEF2 switches from one program to the other, that is, from dendrite- promoting to dendrite-pruning. The discoveries are reported in back-to-back papers in the Feb. 17, 2006 Science.

The uncovering of the MEF2 pathway and its genetic switch helps fill in a theoretical blank in neurobiology, but what excites the researchers are the potential implications for the clinic. "Changes in the morphology of synapses could turn out to be very important in a whole host of diseases including neurodegenerative as well as psychiatric disorders," said Azad Bonni, HMS associate professor of pathology, who, with research fellow Aryaman Shalizi, HST medical student Brice Gaudilliére, and colleagues, authored one of the papers. Graduate student Steven Flavell and Michael Greenberg, HMS professor of neurology at Children's Hospital Boston, who led the other team, believe that the MEF2 pathway could play a role in autism and other neurodevelopmental diseases.

Tiny RNA molecules fine-tune the brain's synapses

70652986 — Mon, 26 Mar 2007 06:24:16 -0400

Non-coding regions of the genome - those that don't code for proteins - are now known to include important elements that regulate gene activity. Among those elements are microRNAs, tiny, recently discovered RNA molecules that suppress gene expression. Increasing evidence indicates a role for microRNAs in the developing nervous system, and researchers from Children's Hospital Boston now demonstrate that one microRNA affects the development of synapses - the points of communication between brain cells that underlie learning and memory. The findings appeared in the Jan. 19, 2006, issue of Nature.

"This paper provides the first evidence that microRNAs have a role at the synapse, allowing for a new level of regulation of gene expression," says senior author Michael Greenberg, director of neuroscience at Children's Hospital Boston. "What we've found is a new mechanism for regulating brain function."

The brain's ability to form and refine synapses allows organisms to learn and respond to their environment, strengthening important synaptic connections, forming new ones, and allowing unimportant ones to weaken. Experiments in Greenberg's lab, done in rats, showed that a microRNA called miR-134 regulates the size of dendritic spines, the protrusions from a neuron's dendrites where synapses form. When neurons were exposed to miR-134, spine volume significantly decreased, weakening the synapse. When miR-134 was inhibited, spines increased in size, strengthening the synapse.

How does the brain reinvent itself?

70652986 — Mon, 26 Mar 2007 05:17:56 -0400

In order for us to use our minds for memory, for learning, and so forth, our brains must continually reinvent themselves. How do they do it? A Harvard Medical School research team has looked at the complicated interactions within nerve cells of ion channels, peptide hormones, growth factors, and a host of regulatory proteins and transcription factors. What they have seen is an amazing dance that requires exquisite timing. Their research was reported in the Oct. 12, 2001, issue of the journal Science. The research team was led by Michael Greenberg, Harvard Medical School professor of neurology at Children's Hospital, and included Ricardo Dolmetsch and other colleagues.

How embryonic stem cells become fine-tuned brains

70652986 — Mon, 26 Mar 2007 05:10:50 -0400

Research by Michael Greenberg, Harvard Medical School professor of neurology at Children's Hospital, begins to explain how the embryonic brain's stem cells decide whether to mature into nerve or glial cells as development proceeds. Greenberg and colleagues reported that neurogenin, a protein known to nudge stem cells toward turning into neurons, does so by actively inhibiting the cells' ability to become astrocytes, a type of glial cell. The study gives researchers trying to develop future therapeutic stem cells a handle on controlling their maturation with more precision.